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THE  SURGICAL  TREATMENT  OF  X-RAY   CARCINOMA 

AND  OTHER  SEVERE  X-RAY  LESIONS.  BASED  UPON 

AN  ANALYSIS  OF  FORTY-SEVEN  CASES 

C.  A.  PORTER,  M.D. 

(Assistant  Professor  of  Surg-ery,  Harvard  Medical  School;  Surgeon  to  the 
Massachusetts  General  Hospital,  Boston,  Mass.) 


THE  PATHOLOGICAL  HISTOLOGY  OF  CHRONIC  X-RAY 
DERMATITIS  AND  EARLY  X-RAY  CARCINOMA 

S.  B.  WOLBACH,  M.D. 

(Director  of  the  Pathological  Laboratory,  Montreal  General  Hospital,  Montreal) 


Reprinted  from 

The  Journal  of  Medical  Research,  Volume  XXI.,  No.  3 

(New  Series,  "Vol.  XVI.,  No.  3),  pp.  357-449,  October,  1909 


BOSTON 

MASSACHUSETTS 

U.S.A. 


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THE  SURGICAL  TREATMENT  OF  X-RAY  CARCINOMA  AND 
OTHER  SEVERE  X-RAY  LESIONS,  BASED  UPON  AN 
ANALYSIS    OF   FORTY-SEVEN   CASES.* 

C.  A.  Porter,  M.D. 

{Assistant  Professor  of  Surgery,  Harvard  Medical  School ;  Surgeon  to  the 

Massachusetts  General  Hospital,  Boston,  Mass.) 

In  the  Annals  of  Surgery  for  November,  1907, 1  published 
the  account  of  two  cases  of  severe  X-ray  lesions ;  one  of 
possible  sarcoma  of  the  finger,  the  other  of  an  X-ray 
operator  who,  since  1896,  in  addition  to  the  severer  forms  of 
dermatitis  and  ulceration,  had  developed,  between   1902  and 

1907,  numerous  carcinomata,  requiring  many  operations, 
amputations,  excisions,  and  skin  graftings.  At  the  time,  I 
was  able  to  gather  the  records  of  ten  other  cases  making, 
with  my  own,  eleven  undoubted  X-ray  cancers,  of  which  six 
had  been  fatal. 

Since  that  time  occasional  reports  of  cases  have  appeared, 
and  three  notable  papers  by  E.  Schumann  ^  in  the  Beitrage 
fUr  Klinische  Chirurgie,  1907,  LXXXIV.,  Heft  3,  page  355  ; 
by  Karl  Lindenborn,^  in  the  same  journal,  1908,  LXXXIX., 
Heft  2,  page  385  ;  and  by  Dr.  Cecil  Rowntree^  of  London 
in    the  Archives  of   the   Middlesex    Hospital,    XHI.,    July, 

1908.  In  all  of  these  papers  new  cases  have  been  pre- 
sented, and  the  etiological  relation  between  X-ray  lesions 
and  carcinoma,  possibly  also  sarcoma,  has  been  thoroughly 
discussed  and,  in  the  case  of  the  former  at  least,  definitely 
proved.  In  the  German  literature  especially,  the  subsequent 
development  of  cancer  upon  lupus  tissue  treated  with  X-rays 
has  aroused  considerable  interest;  though  Steinhans  has  col- 
lected eighty-three  cases  of  carcinoma  following  lupus,  with- 
out X-ray  treatment,  it  seems,  after  a  careful  perusal  of  the 
histories,  at  least  probable  that  the  X-ray  had  a  definite 
influence  upon  the  subsequent  development  of  the  cancer. 
The  cases  can  be  studied  in  detail  in  the  contributions  of 
Schiimann  and  Lindenborn. 

*  Received  for  publication  July  26,  1909. 

(357) 


358  PORTER. 

I  propose  in  this  paper  to  omit  all  consideration  of  the 
lupus  cases,  and  to  limit  myself,  with  very  few  exceptions,  to 
a  consideration  of  the  severer  lesions  which  have  resulted 
from  the  prolonged  action  of  the  X-ray  upon  previously 
healthy  skin,  and  I  should  like  to  emphasize  the  fact  that  not 
only  was  the  skin  healthy,  but  the  wearer  of  it  was  almost 
without  exception  young. 

As  a  result  of  my  former  publication,  I  have  had,  so  far  as 
I  know,  a  unique  experience,  having  operated  upon  eleven 
other  cases  in  addition  to  further  operations  upon  both  of 
the  cases  previously  reported.  Thirteen  in  all :  of  these 
three  were  non-malignant,  two  beginning  carcinoma,  six 
carcinoma,  one  sarcoma(?),  another  carcinomia  or  sarcoma. 
The  distinctions  between  the  phrases  precancerous  and 
beginning  epithelioma  must  of  course  be  a  matter  of  opinion, 
but  the  clinical  histories  of  other  similar  cases  in  this  X-ray 
series  seem  to  show  that  tissues  which  presented  a  precan- 
cerous condition  or  commencing  epithelioma  at  the  time 
of  excision  would,  unless  adequately  treated,  subsequently 
develop  into  squamous  celled  carcinoma.  From  my  experi- 
ence it  seems  almost  assured  that,  given  lesions  of  a  sufficient 
duration  and  severity  without  adequate  treatment,  the  future 
development  of  cancer  can  be  predicted. 

Though  the  harmful  results  of  continuous  exposure  to  the 
X-rays  were  unknown  to  the  early  workers  in  this  field,  it  would 
seem  that  unwittingly  they  have  given  us  the  best  demon- 
stration yet  known  of  the  artificial  or  experimental  produc- 
tion of  cancer.  It  is  unlikely  that  old  age  itself,  with  its 
accompan}-ing  skin  atrophies,  even  if  combined  with  expos- 
ure to  such  various  noxious  influences  as  sea  life,  raw  winds, 
powerful  actinic  rays,  soot  or  paraffin,  would  give  such  an 
example  of  malignant  skin  degeneration  as  seems  so  fre- 
quently to  result  from  protracted  exposure  to  the  X-ray. 
When  it  is  remembered  that  these  lesions  have  been  pro- 
duced in  young  men  at  an  age  when  skin  cancer  is  extremely 
rare,  its  occurrence  is  all  the  more  striking. 

I  have  gathered  from  the  literature,  and  especially  through 
the  kindness  of  physicians  whose   names  will  be   mentioned 


SURGICAL  TREATMENT   OF   X-RAY   CARCINOMA.  359 

with  their  personal  communications,  combined  with  my  own 
experience,  the  records  of  forty-seven  cases  of  severe  X-ray 
lesions.  This  number  in  no  way  represents  the  actual 
figures,  for  there  are  surely  very  many  cases  both  of  serious 
damage  and  also  of  carcinoma  which  have  .  not  been 
reported,  and  are  therefore  not  available.  For  example. 
Dr.  Pusey  of  Chicago  states  : 

"I  have  seen  many  cases  of  this  kind;  certainly  more  than  a  score. 
They  are  all  of  one  kind  and  may  be  briefly  characterized  in  a  group.  As 
a  result  of  either  an  acute  or  more  frequently  of  a  chronic  long  continued 
X-ray  dermatitis,  the  skin  becomes  atrophic,  thinned,  and  harsh,  with  a 
number  of  dilated  blood  vessels  coursing  through  it  and  many  keratoses 
forming  upon  it.  These  keratoses  very  frequently  become  the  site  of 
epithelioma.  In  my  judgment,  the  condition  is  analogous  to  senile 
atrophy  of  the  skin  and  on  the  basis  of  this  analogy  I  prophesied,  before 
the  report  of  any  epithelioma  in  these  cases,  that  epithelioma  would 
develop  in  them.  At  the  start  these  X-ray  epitheliomata  ought  theoreti- 
cally to  be  very  easily  handled,  just  as  the  superficial  epitheliomata 
beginning  in  senile  keratoses  are  very  easily  handled  and  this  has  proved 
true  in  my  experience.  In  my  judgment  these  epitheliomata  should  be 
handled  in  exactly  the  same  way  as  epitheliomatous  senile  keratosis,  either 
by  excision  or  by  some  other  destriictive  procedure.  Many  such  lesions 
have  been  excised  upon  my  advice  with  good  result.  Many  others  that 
were  very  superficial  I  have  treated  by  destruction,  usually  with  carbon 
dioxide  snow.  The  reason  for  this  sort  of  procedure  is  that  it  does  not 
require  the  destruction  of  as  much  tissue  as  a  thorough  excision  and  some- 
times, of  course,  this  is  a  matter  of  importance." 

Dr.  Hyde,  in  addition  to  the  cases  recorded,  says  that  he 
has  seen  at  least  six  other  patients  in  a  precancerous  stage. 
The  experience  of  these  dermatologists  is,  no  doubt,  equalled 
by  some  in  this  and  other  countries,  so  that  the  cases 
reported  are  by  no  means  an  index  of  the  number  of  persons 
who  are  now  suffering  from  early  exposures.  From  France, 
so  far  as  I  am  aware,  there  has  been  no  report  of  serious 
X-ray  lesions. 

Of  these  forty-seven  cases,  four  of  my  own  were  not 
unusual  and  are  reported  simply  for  record.  Four  were 
described  as  in  a  precancerous  stage  or  beginning  epithe- 
lioma; thirty-six  were  undoubted  epidermoid  cancer,  and 
two  of  my  own,  questionable  sarcomata.      Had  it  not  been  for 


360  PORTER. 

the  reports  of  sarcomata  by  other  observers,  especially  in  con- 
junction with  the  X-ray  treatment  of  lupus,  these  two  cases 
would  be  open  to  more  question.  As  it  now  stands,  it  seems 
probable  that  the  X-rays  may  be  a  factor  in  the  production  not 
only  of  cancer,  but  of  sarcoma.  Of  the  thirty-six  cases  of 
epidermoid  cancer,  nine  have  died;  a  mortality  of  twenty- 
five  per  cent,  showing  I  think  quite  clearly  that  these  X-ray 
carcinomata  are  as  malignant,  if  not  more  so,  than  the 
epitheliomata  which  ordinarily  grow  in  the  skin  of  older 
persons,  and  are,  if  allowed  to  advance  beyond  a  certain 
stage,  prone  to  early  metastasis. 

In  the  histories  of  these  cases,  the  reader  will  be  struck  by 
the  period  of  incubation,  if  so  it  may  be  called,  which  dates 
from  the  occurrence  of  the  original  severe  lesions,  or  early 
unprotected  exposures  to  the  rays,  during  which  time 
characteristic  changes  have  taken  place  in  the  skin  and 
underlying  tissues,  which  precede  the  development  of  a 
cancer.  This  period  varies  from  three  to  eleven  years 
(Case  XXII.),  usually  from  five  to  seven,  and  is  dependent 
no  doubt  upon  the  number  of  the  exposures  and  the  vulner- 
ability of  the  individual. 

While  progressive  and  characteristic  lesions  have  developed 
siiice  the  dangers  of  the  X-ray  were  recognized,  and  some 
precautions  were  taken,  it  is  among  those  who  did  the  earliest 
work  that  we  have  had  the  greatest  number  of  fatalities  and 
the  most  severe  lesions  ;  and  this  without  regard  to  the  middle 
age  or  youth  of  the  individuals.  It  has  seemed  that  the 
development  of  the  photographic  plates  combined  with  X-ray 
work  has  led  to  earlier  and  more  serious  lesions  than  when 
X-ray  work  was  done  alone.  We  have,  then,  quite  clearly 
differentiated  from  other  skin  diseases  a  definite  occupation 
dermatosis  which  can  be  diagnosed  at  a  glance,  and  in  the 
chronic  form  resembles  no  other  skin  afTection  known  to  me. 
The  dry  thickened  skin,  without  hairs,  the  telangiectases,  the 
ribbed  nails,  the  keratoses  on  the  backs  of  the  hands  in  young 
men  are  together  pathognomonic,  and  show  the  results  of  the 
specific   action    of    the    X-ray;    in    a    more   advanced   stage, 


SURGICAL   TREATMENT   OF   X-RAY    CARCINOMA.         36 1 

paronychia,  more  numerous  keratoses,  rhagades  and  ulcera- 
tions which  alternately  heal  and  break  down,  until  finally 
there  comes,  as  inevitably  as  fate,  the  development  of  epi- 
thelioma at  the  base  of  a  persistent  or  inflamed  keratosis,  or 
in.  a  chronic  ulcer.  While  the  keratoses  in  no  way  differ  from 
the  usual  senile  condition,  the  combination  of  juvenile  kera- 
toses with  ulceration  of  the  skin  of  the  dorsum  of  the  hands 
and  fingers  seems  peculiar  to  X-ray  dermatoses.  I  have  not 
yet  seen  an  X-ray  lesion  of  the  palmar  surface  of  the  hands 
or  fingers.  Either  the  thickened  skin  offers  some  immunity, 
or  what  is  more  probable,  the  dorsum,  from  the  position  of 
the  hands  in  work  either  with  the  fluoroscope  or  otherwise,  is 
more  exposed.  The  base  of  the  middle  finger  seems  to  be 
the  place  most  universally  affected.  This  knuckle  is  obviously 
most  exposed  and  nearest  to  the  tubes.  The  thumb,  while 
the  nail  and  the  ulnar  border  is  occasionally  affected,  is  to 
some  degree  protected  in  most  exposures  by  the  thick  palmar 
skin.  The  nails  suffer  relatively  early,  and  the  changes  are 
to  some  degree  permanent.  An  accidental  discovery  in  the 
case  of  J.  G.,  Case  XVIII.,  seems  to  show  the  value  of  pro- 
tection during  the  early  years  of  work,  and  the  lack  of  harm- 
ful influence  to  recent  exposures  with  proper  precautions.  A 
broad  gold  ring  was  worn  during  the  first  two  years  of  work 
on  the  ring  finger  of  the  left  hand.  This  was  subsequently 
removed.  The  whole  dorsum  of  the  hand  shows  the  character- 
istic changes,  while  the  skin  protected  by  the  ring  remains  to 
this  day  perfectly  normal.  The  immunity  which  even  light 
clothing  offers  is  shown  by  the  rarity  or  slight  degree  of 
dermatitis  above  the  cuffs,  and  in  those  parts  of  the  body 
protected  by  clothing.  It  would  seem,  therefore,  in  view  of 
this  immunity  from  slight  covering,  that  not  the  X-ray 
themselves,  but  other  emanations  from  the  tube  are  to  be 
held  chiefly  responsible  for  the  burns  and  the  chronic  der- 
matitis. With  these  few  general  remarks,  I  shall  proceed  to 
record  the  cases,  with  the  pathological  reports  when  avail- 
able, and  to  give  after  each  one  a  brief  summary  in  which 
any  interesting  feature  will  be  mentioned. 


362  PORTER. 

Case  I.  —  Miss  A.  Personal  communicafion  fiiom  physidan.  Owing 
to  slight  tabercolons  disease  of  the  anUe,  patient  was  subjected  to  vigor- 
oos  X-rar  treatment  for  a  year  and  a  half.  Extensive  X-ray  bum  resulted 
in  an  intractable  deep  ulceration  3x2  inches  in  extent,  just  above  the 
ankle  on  the  inner  side  of  the  leg.  Pain  was  extreme.  Amputation  at 
point  of  election,  wound  healing,  but  pain  in  stump  persisting  a  year  after 
operation.    No  evidences  of  carcinoma  in  the  ulcer. 

Comment:  Exdsion  and  skin  grafting  mi^t  have  been  done  in  this 
instance  bat.  owing  to  the  tabercolosis  of  the  tarsus,  amputation  seemed 
preferable. 

Case  II.  —  ?er=o::a'..  Dr.  VVolbach,  Case  I.  F.  M.  :  age  55:  was 
operated  upon  :':-  aze- ::ar:iiionia  of  the  s::  — ;:-  v.ith  partial  gastrec- 
tomy, Dec.  19.  :;'.':  re:- very  was  perfec:  '  :Iy  23,  1908,  after 
swallowing  bisrr.-;:-. .  .e  i;  -  ;.'.;aed  for  t::  :/:-  :-an  twenty  minutes 
with  the  fluoro5:::e.  -.>.e  v_.e  .eiDg  suppose:^  a:  a  distance  of  fifteen 
inches.  In  three  we  e  /:  s  -  e  r  e  1 : : :  =-.  'I  : :  rr. :. ! ;. :  -  i  r.  'c  '. :  -  e  .  e  re  pain  an d  an  area 
of  erythema  about  tr.e  =ize  .:  a  z:.:.:.--  \\^.-.  ir.  :.e  rr:d  die  of  the  back. 
This  was  treated  wi:'  :r.e  :.  t:  len:.  ;:r..'  :!  ■  a;- .  .-  :- extreme  suffer- 
ing, the  skin  broke  c:  r. .  :::-;  .^  ar.  :-,  .a;  u  :t-  \  :  -:  .rree  inches  by 
two,  which  was  resJsia- :  :.  a  .     rta.v-  ..    ar.     -   .a:      r.:rea--I  in  size. 

Operation  under  ether,  i«iov.  18,  1900,  M;.  ;ac  .  .se.:-  e  era'  Hospital. 
In  the  center  of  the  back,  over  an  area  i,t.  '•'-  ih  :r.:r.es,  is  a  superficial 
ulcer,  surrounded  by  an  irr^^ular  margin  of  reddened  skin,  situated  over 
the  last  two  dorsal  and  first  two  lumbar  vertebrae.  The  base  oi  the  ulcer 
is  slightly  depressed,  showing  no  evidence  of  granulation  tissue,  but  the 
sur&ce  is  covered  with  firmly  adherent  fibrin.  There  are  several  roundish, 
moundlike  elevations,  varying  in  diameter  from  a  quarter  to  a  half  inch. 
After  careful  preliminary  cleansing,  the  whole  area,  with  a  margin  of 
three-quarters  of  an  inch,  was  excised  down  to  the  imdeiiying  muscle. 
The  choice  then  arose  as  to  a  plastic  operation  or  a  skin  graft ;  the  former 
was  chosen.  A  flap  was  made  with  the  base  uppermost,  extending  down- 
ward and.  to  the  right.  This  was  dissected  up  and  turned  over,  and 
sutured  without  tension  to  the  margins  of  the  wound.  Another  flap  was 
swung  from  below  into  the  denuded  area;  appronmation  was  almost 
complete.  In  a  few  days  the  wound  became  infected  fi-om  a  nearby  fiirun- 
culosis  and,  in  spite  of  vaccines,  there  occurred  some  sloughing  of  the  distal 
part  of  the  flap.  Healing  took  place  slowly,  but  without  fever.  Super- 
ficial necrosis  of  the  surrounding  sldn  is  still  taking  place,  and  raw  sur- 
faces being  covered  with  a  characteristic  fibrinous  membrane.  On  Decem- 
ber 22,  the  patient  was  temporarily  discharged  fi'om  the  hospital,  the 
depth  of  the  wound  granulating  healthily,  but  the  skin  still  undergoing 
superficial  necrosis. 

Summary :  X-ray  bum  after  long  exposure,  July  23,  1908.  Ulceration 
began  six  weeks  afterwards,  steadily  progressing  with  g^reat  pain  in  spite 
of  treatment.  Excision  of  large  ulceration  on  back  on  Nov.  18,  1908. 
Operation  brought  about  immediate  and  permanent  relief  fi'om  pain,  but 


SURGICAL  TREATMENT   OF   X-RAY   CARCINOi\L\. 


0"0 


subseqaent  necrosis  of  the  edges  of  the  wound  raised  the  question  as  to 
whether  the  excision  had  been  adequate.  Whether  the  sloughing 
of  the  flap  was  due  to  infection  or  to  inadequate  blood  supply,  on 
account  of  the  obiiterative  endarteritis  present,  is  an  open  question. 
There  are  other  instances  of  the  sloughing  of  flaps  where  the  .^^kin  has 
been  for  a  long  time  exposed  to  X-rays.  This  at  least  would  sene  as 
a  warning  in  the  performance  of  plastic  surgery  in  these  cases,  and  were  I 
to  operate  again  I  should  simply  excise  such  an  ulcer  with  primary  skin 
grafting.  The  mounds  mentioned  on  the  surface  of  the  ulcer  were  shown 
by  microscopic  examination  to  be  blisters  in  the  deep  layers  of  the 
epidermis. 

Pathological  report  by  Dr.  Wolbach.  Material  consists  of  Zenker  hard- 
ened tissue  representing  a  large  ulcer  about  lo  centimeters  in  diameter 
surrounded  by  a  border  of  epidermis  i  to  i^  centimeters  in  thickness. 

Microscopic  description:  paraffine  sections:  phosphotungstic  and 
hematein  stain. 

The  portions  covered  by  skin  are  very  similar  in  appearance  to  the  tissue 
from  the  cases  6f  IVfiss  H.  and  Mr.  S.,  that  is,  we  have  the  same  rarefica- 
tion  of  the  corium  immediately  beneath  the  epidermis.  The  papillje 
are  absent,  so  that  the  epidermis  presents  a  perfectly  smooth  under  sur- 
face.  The  portion  denuded  of  epithelium  shows  a  slight  fibrinous  exudate 
overlying  the  corium.  In  a  few  places  there  is  granulation  tissue  beneath 
thick  layers  of  coarse  meshed  fibrin.  The  epidermis  in  places  is  mark- 
edly thinned  and  the  ordinary  arrangement  of  the  basal  layer  is  lost. 
The  cells  of  the  epidermis  in  the  thin  portions  are  larger,  somewhat  ves- 
icular in  character  and  stain  less  deeply  than  those  of  normal  epidermis. 
There  is  nowhere  any  evidence  of  invasion  of  the  corium  by  epidermis. 
The  deep  vessels  of  the  corium  show  very  slight  changes.  There  are 
many  coil  glands  which  are  practically  normal.  Others  are  atrophic  and 
are  surrounded  by  new  formed  connective  tissue  and  masses  of  lymphoid 
and  plasma  cells.  No  hair  follicles  or  sebaceous  glands  found  in  the  sec- 
tion. Irregular  areas  and  tracts  throughout  the  corium  filled  with 
lymphoid  and  plasma  cells  are  probably  spaces  once  occupied  b}^  coil 
glands  and  ducts. 

In  brief,  this  tissue  sho^i^  the  same  processes  found  in  Case  VIII. 
and  Case  IV.,  but  to  a  less  advanced  degree.  The  characteristic  changes 
of  the  corium  are  present.  Vessels  show  very  slight  thickening  of  the 
intima.  Epidermis,  however,  does  not  show  irregular  downgrowth  sug- 
gesting beginning  carcinoma. 

Case  III.  —  Personal.  Dr.  Wolbach,  Case  II.  E.  R. ;  28  years 
(female) ;  referred  to  me  by  Dr.  Reeves  of  Boston.  Patient  con- 
sulted Dr.  R.  first  for  ulcerations  of  elbow  and  knee  on  March  18, 
1908.  X-ray  treatment  until  the  end  of  April  at  the  Emergency  Hos- 
pital, when  they  broke  down  and  she  went  to  the  Emergency  as  a 
patient  for  three  weeks,  as  ulcers  formed  on  both  knee  and  elbow. 
Under  treatment,  the  acute  dermatitis  subsided,  but  since  then  the  ulcers 


364  PORTER. 

have  never  healed.  While  at  hospital  the  ulcer  diminished  on  the  knee 
from  5x3  inches  to  2^  x  i  ;  that  on  the  elbow  from  2^x1^  to  the  size  of  a 
•'  quarter."  Patient  worked  for  two  weeks,  and  although  the  ulcerations  did 
not  increase  in  size,  the  skin  surrounding  them  became  irritated.  Was 
again  admitted  to  hospital  for  three  weeks  in  June ;  improvement  under 
rest  and  treatment.  Reentered  August  18,  where  she  remained  until 
Nov.  7,  1908,  when  she  was  discharged.     Daily  dressing  since  then. 

Examination  Dec.  4,  1908.  Over  inner  aspect  of  flexure  of  elbow  are 
characteristic  X-ray  changes ;  evidences  of  old  ulceration  about  4x3 
with  cicatricial  tissue  and  telangiectases.  Just  above  the  inner  condyle  is 
an  ulceration  about  size  of  a  dime  which  is  covered  with  a  yellow,  fibrin- 
ous scab.  The  skin  about  it  is  atrophic;  causes  pain  on  motion  ;  no  der- 
matitis. Examination  of  left  leg :  dermatitis  from  middle  of  thigh  to 
top  of  boot ;  a  great  deal  of  irritation  and  itching.  There  is  some 
edema.  On  the  outer  side  of  the  knee  over  an  area  6x5  inches  the  skin  is 
reddened,  pigmented  and  shows  scars  peripherally  to  the  old  healed 
ulcerations  ;  also  telangiectases.  Ulceration  at  present  is  2^  x  i  inches  ; 
sore  and  tender  to  touch.  Pain  and  sensitiveness,  however,  are  less  now 
than  during  acute  inflammation.  Patient  says  boric  acid,  aristol,  corro- 
sive wash,  as  well  as  ichthyol  all  irritated  the  skin.  The  edges  of  the  skin 
show  little  evidence  of  healing ;  there  is  fibrin  at  the  margin  of  the  grow- 
ing epithelium.  The  whole  skin  of  this  area  is  indurated  and  is  two  or 
three  times  the  normal  thickness.  There  is  already  some  tendency  to 
cicatricial  contraction,  but  this  is  on  the  outside  of  the  knee,  not  in  the 
popliteal  space.  The  dermatitis  of  the  rest  of  the  leg  can  be  properly 
called  medicamentosa. 

Operation,  Jan.  21,  1909,  N.  E.  Baptist  Hospital.  Since  last  visit, 
the  patient  has  been  comparatively  free  from  pain,  as  the  dermatitis  has 
subsided,  but  the  ulceration  shows  no  evidence  of  healing  or  of  growing 
smaller.  Its  base  is  very  much  indurated.  Under  ether,  thorough  exci- 
sion down  to  fat,  with  half-inch  margin.  After  bleeding  had  stopped  raw 
surface  was  covered  with  Thiersch  grafts  from  the  left  thigh.  Protective 
tissue  ;  firm  pressure  ;  splint. 

Jan.  28,  1909.  First  dressing.  Little  maceration;  five-sixths  of  the 
grafts  have  taken,  but  here  and  there  in  the  edges,  and  in  one  or  two 
places  in  the  center,  there  have  been  small  hemorrhages  with  resulting 
necrosis. 

Jan.  30,  1909.     Grafts  exposed  to  air  and  apparently  doing  well. 

Feb.  24,  1909.  Almost  all  of  the  grafts  took,  but  here  and  there,  one' 
or  two  small  areas  subsequently  broke  down  and  showed  a  tendency  to 
spread.  It  would  seem  to  me  as  if  excision  had  been  inadequate  and 
further  operation  was  advisable.  This  proves  to  me  quite  clearly,  in  con- 
nection with  the  S.  case,  that  it  is  hard  to  gauge  how  much  devitalized 
tissue  should  be  removed  ;  although  my  excisions  have  appeared  at  the 
time  free  enough,  I  think  in  general  they  may  have  been  inadequate. 

March  25,  1909.  As  there  had  been  a  previous  history  of  specific  dis- 
ease in  this  case.  I  decided  to  try  the  effects  of  internal  treatment  before 


SURGICAL   TREATMENT   OF   X-RAY   CARCINOMA.         365 

resorting  to  further  grafting.  After  ten  days  of  mixed  treatment  and  the 
local  application  of  black  wash,  the  broken-down  areas  were  entirely 
healed  over.  It  would  thus  seem  as  if  the  original  ulcerations,  for  which 
the  X-rays  had  been  applied,  were  undoubtedly  specific,  and  that  in  spite 
of  grafting  the  disease  progressed  from  a  lower  level. 

April  I,  1909.  Patient  is  entirely  free  from  pain.  Grafts  are  beginning 
to  be  mobile ;  the  leg  is  soundly  healed. 

For  pathological  report  see  Dr.  Wolbach's  paper  under  Case  II. 

Case  IV.  —  Personal.  Dr.  Wolbach,  Case  III.  F.  H.  S. ;  40  years; 
referred  to  me  by  Dr.  C.  J.  White  Nov.  16,  1908.  Treatment  with 
X-rays  five  years  ago,  for  eczema  of  both  legs,  with  marked  improvement. 
After  subsequent,  rather  frequent  treatments,  extending  over  a  period  of 
a  year,  there  developed  a  rather  severe  dermatitis  which  healed  slowly 
with  complete  desquamation  of  the  superficial  layers  of  the  skin  from  the 
middle  of  the  thighs  downward.  Four  years  ago  there  appeared  on  the 
inner  side  of  the  left  calf  a  small  ulcer,  which  from  that  time  has  never 
completely  healed.  On  the  right  shin  there  was  also  an  ulcer  which  took 
months  to  heal.  Both  popliteal  spaces  showed  characteristic  telangiec- 
tases. There  has  been  no  pain.  In  August,  1908,  the  ulceration  of  the 
left  leg  began  to  spread  rapidly  and  refused  to  yield  to  any  treatment ; 
radium  was  twice  applied.  Examination  on  Nov.  16,  1908,  shows  about 
the  middle  of  the  left  leg  an  ulceration,  3  x  2|  inches.  The  edges  are 
irregular,  slightly  indurated ;  in  some  parts  there  are  islands  of  growing 
epidermis,  and  in  others  fairly  healthy  areas  of  granulation  —  in  still 
others,  there  is  an  unhealthy  surface  covered  with  adherent  fibrin.  The 
skin  is  undermined  and  shows  no  evidence  of  repair.  Operation  was 
advised  and  accepted. 

Operation  under  ether,  Nov.  19,  1908.  Leg  was  disinfected  with 
extreme  care  and  the  whole  ulcer  excised  with  a  margin  of  half  an  inch 
down  to  the  subcutaneous  fat  and  under  the  old  ulceration  to  the  sheath 
of  the  gastrocnemius  muscle  itself.  After  bleeding  had  ceased  the 
wound  was  again  disinfected  and  moderately  thick  skin  grafts  were  taken 
from  the  left  thigh.  These  were  stitched  to  the  edges  and  wound  covered 
with  protective  and  a  firm  bandage.  On  the  evening  following  operation 
the  temperature  rose  to  loi,  but  he  had  no  pain.  At  noon  on  the  follow- 
ing day  the  wound  was  dressed,  the  temperature  being  at  that  time  100. 
It  was  found  that  infection  had  taken  place,  and  that  the  periphery  of 
the  grafts  had  sloughed  with  some  hemorrhagic  infiltration  into  the 
central  portion.  In  spite  of  exposure  to  air,  alternating  with  antiseptic 
fomentations,  all  of  the  grafts  separated,  except  for  an  irregular  area 
about  three-fourths  of  an  inch  in  diameter,  in  the  very  center  of  the 
wound.  At  the  end  of  two  weeks  the  wound  became  healthy,  and  granu- 
lation was  well  established.  Small  Thiersch  grafts  from  another  patient 
were  placed  on  the  surface,  but  in  two  days  all  of  these  except  two  had 
likewise  sloughed  ;  in  the  meantime  there  had  been  an  unusual  amount  of 
suppuration  of  the  thigh  from  which  the  grafts  had  originally  been  removed. 


366  PORTER. 

The  lower  edge  of  the  wound,  where  the  skin  was  twice  the  normal  thick- 
ness, showed  no  evidence  of  healing.  While  infection  probably  played 
the  chief  role  in  this  failure,  it  seemed  to  me  not  unlikely  that  the  tissues 
both  of  the  thigh  and  of  the  leg  were  less  resistant  owing  to  the  previous 
X-ray  injuries.  On  several  occasions,  small  strips  of  skin  were  placed 
upon  the  wound  and  covered  with  cr^pe  lisse.  These  grafts  with  the 
rapid  growth  of  the  original  Thiersch  graft  in  the  middle  allowed  the 
patient  to  return  to  his  home  on  Dec.  22,  1908,  with  the  wound  four-fifths 
healed. 

Pathological  report  by  Dr.  S.  B.  Wolbach.  A  large  piece  of  Zenker 
hardened  tissue  consisting  of  an  ulcer  with  surrounding  skin.  Microscopic 
examination :  Zenker  fixation  ;  paraffine  sections ;  phosphotungstic  acid- 
hematein  stain. 

The  tissue  is  very  similar  to  that  from  the  case  of  Miss  H.  The  ulcer- 
ated surface  shows  typical  granulation  tissue  springing  from  a  base  of 
rarefied  corium.  On  the  surface  are  small  islands  of  epithelium  which 
present  no  striking  or  unusual  characteristics.  The  most  striking  changes 
found  in  the  sections  are  in  the  corium  just  beneath  the  epidermis  sur- 
rounding the  ulcer  and  in  the  vessels  throughout  the  sections.  The  con- 
nective tissue  cells  of  the  corium  just  beneath  the  epidermis  are  widely 
separated  and  of  embryonic  type  in  appearance ;  they  are  surrounded  by 
very  few  delicate  collagenous  fibrils.  In  this  rarefied  corium  are  many 
large  blood  vessels  lined  with  a  single  layer  of  endothelium.  A  few  of 
these  vessels  lie  in  direct  contact  with  the  basal  layer  of  the  epidermis, 
some  are  completely  surrounded  by  epidermis  and  a  few  are  filled  with 
fibrin  thrombi. 

In  the  deep  layers  of  the  corium  there  is  marked  thickening  of  the  walls 
of  both  arteries  and  veins.  The  thickening  is  due  chiefly  to  an  increase 
in  the  connective  tissue  of  the  intima.  The  endothelium  of  some  vessels 
is  swollen.  There  is  also  an  increase  of  connective  tissue  in  the  muscular 
coats.     There  are  numerous  completely  obliterated  arteries. 

The  coil  glands  are  nearly  completely  absent.  A  few  atrophic  tubules 
are  found  in  areas  of  new  formed  connective  tissue.  No  hair  follicles  or 
sebaceous  glands  are  to  be  found.  The  epidermis  surrounding  the  ulcer 
is  slightly  thickened.  The  horny  layer  is  strikingly  narrow  and  in  places 
absent.  There  are  many  irregular  downgrowths  of  epidermis  into  the 
rarefied  corium,  but  these  processes  all  present  an  orderly  layer  of  colum- 
nal  basal  cells.  At  the  edge  of  the  ulcer  are  downgrowths  of  atypical 
epithelium,  not  however  more  striking  than  in  the  case  of  any  chronic 
ulcer. 

There  is  nowhere  any  suggestion  of  malignancy  or  actual  invasion  of 
the  corium. 

Subsequent  history:  Feb.  i,  1909.  Upon  returning  to  his  home,  the 
wound  was  completely  healed  in  three  or  four  days,  but  on  January  2  the 
grafts  which  had  been  taken  from  another  patient  .slowly  broke  down 
with  the  formation  of  blisters,  and  upon  his  arrival  in  Boston  had  entirely 
disappeared.     The  under  surface,  however,  was  healthy,  and  in  two  days 


SURGICAL   TREATMENT   OF   X-RAY    CARCINOMA.         367 

snips  were  applied  from  liis  arm  and  covered  witti  crepe  lisse.  Tliese 
grafts  rapidly  coalesced  by  January  20,  and  he  was  discharged  home 
entirely  healed  and  has  so  remained  until  the  present  time. 

Case  V.  —  Personal.  W.  H.  M.  (physician),  Lawrence,  Mass.;  43 
years.  Patient's  hands  have  been  treated  by  the  X-rays  for  seven  years,  for 
eczema;  exposures  ten  to  fifteen  minutes  —  both  coil  and  static  machines. 
Extensive,  rather  superficial  burns  of  both  hands  in  January,  1906;  the 
skin  sloughed  off  but  was  replaced.  Later  exposures  in  May,  1906,  followed 
by  slight  dermatitis.  Last  exposure,  Dec.  10,  1906,  static  machine,  five 
inches,  twelve  minutes,  followed  by  swelling  of  hands,  and  in  four  days, 
with  small  cracks  at  knuckle  of  index  finger  of  right  hand.  Black  spots  on 
all  sides  of  the  fissure.  Continual,  though  gradually  increasing  ulceration 
with  no  tendency  to  heal.  Pain  has  been  excessive,  cutting  down  his 
sleep  to  an  average  of  two  hours  a  night ;  unrelieved  by  anything  except 
morphia. 

Examination  of  right  hand  shows  characteristic  X-ray  lesions,  few  kera- 
toses and  many  telangiectases.  Over  the  knuckle  of  index  finger  is  an 
ulceration  with  slightly  indurated  edges,  about  3x4  centimeters.  On  the 
dorsum  of  the  first  phalanx,  same  finger,  is  another  ulceration  about  the 
size  of  the  little  finger  nail.  There  are  several  extremely  tender  points  in 
both  ulcerations.  Owing  to  immobilization  of  the  hand,  there  is  some 
edema  and  little  flexion  of  the  first  and  second  fingers.  (See  Plate 
XXXV.,  Fig.  I.) 

Patient  was  operated  upon  by  me  at  the  Massachusetts  General  Hospi- 
tal May  2,  1907.  With  a  wide  margin,  both  ulcers  were  thoroughly 
excised,  removing  all  of  the  skin  down  to  the  tendons,  and  the  dorsal 
aponeurosis,  and  the  skin  grafted  in  the  usual  manner.  Treated  with  pro- 
tective for  thirty-six  hours,  and  then  exposed  to  air  under  a  cage.  The 
grafts  healed  soundly,  except  for  one  or  two  small  areas  at  the  edge. 
Patient  was  discharged  from  the  hospital  in  ten  days.  Pain  entirely 
ceased  from  the  time  of  operation. 

Pathological  examination  showed  no  definite  carcinoma,  but  in  certain 
spots  the  epithelium  was  clearly  in  a  precancerous  stage.  The  papillary 
layers  were  depressed  below  the  surface,  mitosis  was  well  marked,  and 
there  was  slight  round  cell  infiltration. 

In  August,  1907,  for  the  first  time,  the  slight  ulceration  at  the  edge  of 
the  graft,  near  the  base  of  the  middle  finger,  was  completely  healed. 
There  has  been  no  pain,  and  flexion  in  the  fingers  is  rapidly  returning. 
By  Jan.  i,  1908,  there  was  final  and  permanent  healing;  flexion  normal; 
no  pain. 

March  11,  1908.  Fingers  could  be  flexed  normally,  the  graft  was  mov- 
able on  the  underlying  tissues,  and  appeared  to  be  the  most  normal  skin' 
on  the  back  of  the  hand.  He  still  suffers  from  eczema  of  other  parts  of 
the  skin. 

Summary  :  Treatment  with  X-rays  for  seven  years  for  eczema  of  right 
hand.     Extremely  painful  ulceration  at  base  of  first  and  middle  fingers. 


368  PORTER. 

Average  sleep  for  past  six  months,  without  morphia,  only  two  hours. 
Deep  excision  ;  grafting.  Complete  freedom  from  pain.  Sore  at  edge  of 
graft  unhealed  for  several  months.  Present  condition  :  complete  healing  ; 
normal  motion.     Precancerous  condition,  but  no  definite  epithelioma. 

Case  VI.  —  B.  S.  B.;  X-ray  manufacturer;  personal  communication 
from  Dr.  M.  M.  Johnson,  of  Hartford,  Conn.  Patient  had  severe  X-ray 
burn  of  back  of  left  hand,  and  over  the  middle  of  the  sternum.  The  skin 
of  the  back  of  the  hand  was  thickened,  and  cut  like  leather.  There  were 
many  small  nodules  and  one  large  open  sore,  the  result  of  sloughing.  A 
circular  incision  was  made  around  the  open  sore,  and  the  metacarpal  bone 
and  the  tissues  were  curetted  and  thoroughly  cleaned.  A  Wolf  graft  was 
taken  from  the  arm  and  stitched  in  position.  At  one  time  there  was  indi- 
cation of  sloughing  at  the  border  of  the  transplanted  tissue,  but  eventually 
the  result  was  perfect.  The  small  nodules  were  excised  and  but  few  have 
returned.  The  ulcer  over  the  sternum  was  excised  and  closed  by  granula- 
tion. Microscopic  examination  showed  chronic  inflammatory  tissue,  with- 
out any  trace  of  epithelioma. 

Case  VII.  — Personal.  Dr.  Wolbach,  Case  VI.  W.  W.  G.  (physi- 
cian), of  St.  Louis;  42  years.  Began  using  the  X-ray  in  his  practice  in 
1897;  a  static  machine.  May,  1900,  had  an  itching  dermatitis  on  the 
dorsal  surface  of  the  left  hand ;  this  healed  in  the  course  of  a  few  weeks. 
He  next  noticed,  within  a  short  time,  trophic  changes  about  the  nails, 
especially  that  of  the  index  finger.  There  was  alopecia  ;  the  skin  became 
dry  and  reddened.  In  December,  1900,  infection  about  index  finger 
caused  excruciating  pain,  and  in  March,  190 1,  the  nail  was  removed.  In 
1903  patient  was  in  Berlin,  and  at  that  time  had  numerous  telangiectatic 
areas  on  the  dorsum  of  hand  and  fingers,  as  well  as  several  keratoses. 
Owing  to  persistent  ulceration  about  the  matrix  of  the  first  finger  nail,  the 
finger  was  amputated  through  the  middle  phalanx  by  Professor  Sonnen- 
berg.  Since  then  other  ulcerations  have  developed,  the  most  annoying  at 
the  base  of  the  middle  finger.  This  remained  open  until  January,  1905, 
when  it  was  excised  by  Dr.  Bernays,  and  a  Krause  graft  implanted ;  the 
graft  healed  well.  Following  this  operation  he  had  but  little  pain  but  was 
frequently  annoyed  by  superficial  ulcerations  about  the  fingers.  For  a 
year  or  more,  prior  to  December,  1907,  he  suffered  from  a  slight  ulcera- 
tion near  a  keratosis  at  the  base  of  the  ring  and  little  fingers.  There  was 
also  painful  ulceration  about  the  matrix  of  the  little  finger  nail.  On  Dec. 
22,  1907,  Dr.  Willard  Bartlett  operated  under  ether.  The  middle  finger 
was  amputated,  through  the  second  phalanx,  several  ulcerations  at  the 
base  of  ring  and  little  fingers  excised  and  the  skin  sutured.  An  attempt 
was  made  to  extirpate  the  matrix  of  the  radial  half  of  the  little  finger  nail. 
At  the  same  time,  Thiersch  graft  was  implanted,  after  excision  of  a  painful 
fissure  over  the  distal  portion  of  the  proximal  phalanx  of  the  ring  finger; 
the  Thiersch  graft  was  a  success.  Except  for  frequent  slight  injuries  to 
the   dorsal  surfaces   of  the    fingers,    which    healed   promptly,    the   hand 


SURGICAL   TREATMENT   OF   X-RAY   CARCINOMA.         369 

remained  practically  free  from  further  ulceration  until  April,  1908,  when 
an  ulcer  developed  beneath  a  keratosis  near  the  proximal  end  of  the 
middle  phalanx  of  the  ring  finger  which,  like  all  the  other  ulcerations,  was 
exceedingly  painful  at  times.  The  skin  about  the  thumb  remained 
throughout  practically  free  from  lesions,  except  for  a  horny  growth  over 
the  inner  surface  of  the  proximal  phalanx.  There  had  never  been  serious 
trophic  disturbances  of  the  thumb  nail,  but  the  finger  nails,  in  order  of 
severity,  from  index  to  little  finger,  were  profoundly  affected.  The  kera- 
totic  spots  have  invariably  been  the  seat  of  the  ulcerations,  excepting  that 
on  the  amputated  index  finger  which  arose  from  retention  of  some  of  the 
nail-producing  membrane. 

Patient  consulted  me  Aug.  17,  igo8.  The  left  hand  is  typical  in  appear- 
ance ;  telangiectases  are  numerous ;  there  are  several  thickened  papules 
over  the  base  of  the  thumb  ;  the  ends  of  two  fingers  have  been  amputated ; 
the  nail  of  the  ring  finger  is  irregular  and  thickened  ;  the  nail  of  the  little 
finger  has  in  part  been  removed,  but  there  has  been  persistent  ulceration 
on  the  radial  side  of  the  matrix  which  is  extremely  sensitive.  There  is 
an  open  ulceration,  without  indurated  margins,  over  the  first  interphalangeal 
joint  of  the  ring  finger.  There  is  moderate  motion  in  this  joint ;  the 
last  joint  is  hyperextended  and  somewhat  stiff.  On  the  backs  of  the 
other  three  fingers  are  areas  of  keratoses,  scar  tissue,  and  occasional 
petechiae.  At  the  base  of  the  cleft,  between  the  thumb  and  first  finger, 
is  an  ulcerated  papule  with  somewhat  indurated  edges. 

Operation  under  ether,  Aug.  19,  1908.  Several  small  papules  were 
excised  ;  the  wound  sutured  with  horse  hair.  The  ulcerated  area  on  the 
ring  finger  was  carefully  excised  with  a  wide  margin  down  to  the  dorsal 
aponeurosis ;  the  edges  were  bevelled  as  usual ;  bleeding  was  profuse. 
The  ulcerated  hemorrhagic  and  keratotic  areas  on  the  backs  of  the  other 
fingers  were  also  excised,  as  were  several  keratoses  in  other  parts  of  the 
hand.  The  entire  matrix  of  the  little  finger  was  thoroughly  removed  and 
a  graft  applied.  Moderately  thick  grafts  were  cut  from  the  arm  and 
sutured  in  position  after  the  bleeding  had  ceased.  Hand  was  carefully 
strapped  to  a  well-padded  splint,  rubber  tissue  placed  in  an  imbricated 
fashion  over  the  grafts.  Firm  pressure  with  large  gauze  dressing  applied. 
The  operation  lasted  about  two  hours  and  a  quarter. 

At  the  end  of  thirty-six  hours  the  protective  was  removed,  the  hand 
greased  with  a  mixture  of  benzoated  lard,  lanolin,  and  ichthyol.  All  the 
grafts,  except  one  on  the  forefinger,  looked  well.  August  23,  grafts 
looked  fairly  well ;  that  on  fourth  finger  improving  in  appearance.  Graft  on 
terminal  phalanx  of  little  finger  dead.  Some  sloughing  of  portions  of 
grafts  on  first  and  middle  fingers.  August  26,  large  part  of  graft  on  fore- 
finger is  sloughing,  and  part  of  that  on  the  middle.  Grafts  on  the  ring 
and  little  fingers  and  dorsum  have  taken  well.  August  29,  grafted  areas 
thoroughly  clean  and  all  portions  of  unattached  skin  were  removed. 
September  12,  all  granulating  areas  are  cicatrizing  rapidly  from  the  edges. 
Discharged  on  Sept.  15,  1908. 


370  PORTER. 

Letter  from  patient,  dated  Oct.  22,  1908  : 

"  It  is  just  a  few  days  more  than  a  month  since  I  took  leave  of  you,  and 
since  that  time  my  hand  has  shown  continuous  improvement.  The  scabs 
have  fallen  from  index  and  middle  fingers,  and  the  slight  cicatrization 
about  these  in  no  way  interferes  with  the  free  mobility  of  the  joints.  There 
is  a  certain  elasticity  about  the  skin  of  these  two  fingers  which  I  have 
not  hitherto  felt.  The  grafts  on  the  other  fingers  and  at  the  base  of  ring 
finger  are  simply  perfect.  Even  the  slight  '  V '  shaped  defect  of  graft  on 
ring  finger  has  filled  in,  so  that  the  entire  surface  is  now  uniform.  There 
has  been  no  sign  of  activity  in  little  finger  matrix,  and  this  more  than  two 
months  since  the  operation,  so  that  I  am  not  anticipating  any  further 
trouble  at  this  point.  The  dorsal  surface  of  the  hand,  with  the  exception 
of  one  little  point,  is  entirely  free  from  keratoses,  and  the  places  where 
such  were  shaved  are  now  smooth  and  pliable  cicatrices  :  indeed,  the 
appearance  of  the  whole  hand  shows  a  vitality  which  I  had  not  dreamed  to 
be  possible."" 

Pathological  report  by  Dr.  S.  B.  Wolbach.  The  sections  show  approx- 
imately normal  epidermis  and  corium,  except  in  the  middle  portion  where 
the  epidermis  is  markedly  thickened,  the  cerium  infiltrated  with  lymphoid 
and  plasma  cells  and  without  papillae.  There  is  a  marked  heaping  up  of 
the  horny  layer  of  the  epidermis,  and  in  one  place  in  the  center,  where  the 
section  is  tangential  to  a  hair  follicle,  there  is  a  downgrowth  of  the  epi- 
dermis into  the  infiltrated  corium.  These  processes  from  the  epidermis 
are  atypical  in  that  the  columnar  regularly  arranged  basal  layer  of  cells  is 
absent,  and  because  of  included  collagen  fibrils.  The  corium  just  beneath 
the  epidermis  does  not  show  the  rarefication  found  in  many  other  sections 
of  X-ray  keratoses.     The  hair  follicles  and  glands  are  practically  normal. 

Siimviary :  Marked  hypertrophy  of  epidermis  with  keratosis  and  begin- 
ning invasion  of  corium  by  epithelium. 

Case  VIII.  —  Personal.  Wolbach,  Case  IV.  Plate  XXXV.,  Figs.  2 
and  3.  Miss  H.,  40  years,  is  one  of  extreme  interest  from  many  points  of 
view.  In  brief,  the  previous  history  is  as  follows :  seven  years  ago, 
patient  was  operated  upon  by  Dr.  Boothby  for  a  so-called  fibroid  of  the 
uterus,  the  operation  being  an  abdominal  hysterectomy.  She  was  well 
for  a  year,  when  there  formed,  to  the  right  of  the  incision,  in  the  abdomi- 
nal wall,  a  slowly  growing  tumor,  which  was.  however,  characteristic  of  a 
sarcoma,  and  pronounced  inoperable  by  Dr.  Maurice  H.  Richardson,  by 
whom  she  was  sent  to  Dr.  W.  B.  Coley  of  New  York  for  treatment  by 
toxins.  He  excised  a  portion  of  the  growth,  and  found  it  to  be  a  fibro- 
sarcoma. At  first  the  growth  diminished  under  toxins,  but  after  ten 
months  it  was  decided  that  further  treatment  was  not  warrantable  as  the 
growth  was  increasing  rapidly.  The  patient  was  losing  flesh,  markedly 
cachectic,  very  weak,  and  complained  bitterly  of  pressure  symptoms.  I 
am  quoting  from  the  report  of  this  case  by  Dr.  Clarence  E.  Skinner  of 
New  Haven,   Conn.,  to   whom  she  was  referred  by  Dr.  Bevan  of  West 


SURGICAL   TREATMENT    OF    X-RAV    CARCINOMA.  37 1 

Haven,  for  roentgenization.  At  this  time,  he  states  that  the  mass 
covered  ten  inches  from  side  to  side  at  the  level  of  the  anterior  superior 
spines  of  the  ilia,  eight  inches  vertically  in  the  median  line,  and 
about  five  inches  antero-posteriorly.  Treatment  was  begun  by  him  on 
Jan.  28,  1902.  and  during  the  next  four  months  she  received  forty-six 
applications.  The  general  condition  began  to  improve  at  once,  but  the 
tumor  showed  little  change.  Patient  went  home  for  a  visit,  and  upon  her 
return  it  was  noted  that  the  tumor  had  diminished  about  one-fifth  in 
size.  From  June  17  to  September  3  she  received  thirty-one  roentgeniza- 
tions.  Her  general  health  continued  to  improve,  and  the  tumor  steadilv 
decreased  in  size,  and  at  the  end  of  this  period  she  resumed  her  school 
teaching. 

In  brief,  then,  the  patient  was  under  treatment  for  two  years  and  three 
months,  receiving,  however,  the  majority  of  her  applications  during  the 
first  eight  months.  The  last  treatment  was  given  on  May  20,  1904,  at 
which  time  no  trace  of  the  tumor  was  discoverable  at  examination  by  Dr. 
C.  A.  Bevan  of  West  Haven,  and  in  July  by  Dr.  W.  B.  Coley  of  New 
York.  The  patient  remained  perfectly  well  until  August,  1907,  though 
she  had  noticed  that  the  skin  of  the  hypogastric  region  was  irregularly 
mottled  and  much  thicker  than  normal,  especially  on  the  right  side. 
Pain,  from  which  she  had  been  free,  began  to  be  severe  and  ulceration 
commenced.  No  treatment  seemed  of  avail,  the  ulcerative  process 
gradually  spreading,  undermining  the  skin,  which  subsequently  necrosed. 
She  lost  weight  and  strength,  becoming  anemic,  and  suffered  severely 
from  the  pain.  She  was  referred  to  me  by  Dr.  Dennett  of  Winchester, 
and  I  first  saw  her  at  the  Baptist  Hospital  on  March  7,  1908.  Examina- 
tion at  this  time  showed  in  the  hypogastric  region  more  on  the  right  than 
on  the  left,  an  irregular,  undermined  ulcer  about  the  size  of  the  palm  of 
one's  hand,  roughly  an  equilateral  triangle,  extending  to  the  right  side  of  the 
pubis,  then  nearly  to  the  right  iliac  spine,  the  other  angle  approaching  the 
umbilicus.  The  base  of  this  ulceration  is  sloughing  in  parts ;  in  others 
presenting  poorly  vascularized  granulation  tissue,  in  which  necrosis  is 
advancing  rapidly.  Several  areas  in  the  surrounding  skin  show  charac- 
teristic appearances.  The  irregular  undermined  ulceration  with  a  firmly 
adherent  fibrinous  base  is  surrounded  by  a  very  bright  scarlet  red  areola, 
which  bleeds  on  the  slightest  touch.  Certain  points  in  the  ulceration  are 
exquisitely  painful  on  pressure.  There  is  slight  fever.  After  attempt- 
ing to  cleanse  wound  with  antiseptics  for  a  few  days  on  March  16,  the 
whole  ulcerated  area,  with  a  margin  of  about  an  inch,  was  excised  down  to 
the  underlying  tissue.  This  excision  left  apparently  normal  fat.  except 
over  an  area  two  by  three  inches  to  the  right  of  the  median  line,  where 
extremely  firm  scar  tissue  marked  the  site  of  the  original  growth.  The 
skin  at  the  periphery,  however,  was  very  tough- and  three  times  the  normal 
thickness.  The  whole  wound  was  thoroughly  disinfected  with  carbolic 
acid,  ninety-five  per  cent  alcohol  and  salt  solution,  and  an  attempt  was 
made  by  tension  sutures  to  diminish  the  gaping  wound.  It  was  dressed 
with  protective  tissue,  gauze,  and  swathe.     The  tissue  was  given  to  Dr. 


372  PORTER. 

Wolbach  of  the    Harv-ard   Medical  School  for  examination.     His   report 
was  as  follows : 

"  The  specimen  consists  of  a  large,  irregularly  triangular  piece  of  skin 
and  subcutaneous  tissue,  its  '  base'  is  9  centimeters,  and  the  sides  are  10 
and  1 1.5  centimeters  respectively;  it  is  from  2  to  2.5  centimeters  in  thick- 
ness, except  at  the  central  portion  where  it  is  .5  to  .7  centimeter  thick. 
The  skin  surface  shows  a  large,  irregularly  triangular  ulcer  (5.2  x  7.5  x  8 
centimeters)  conforming  in  general  to  the  shape  of  the  specimen.  The 
base  of  the  ulcer  is  depressed  from  .2  to  .6  centimeter  below  the  rough, 
irregular,  ragged,  overhanging,  and  undermined  non-indurated  edges 
which  are  necrotic,  reddish  gray  in  color,  and  bathed  in  bright  yellow 
purulent  exudation. 

"  The  base  of  the  ulcer  is  bright  red  to  grayish  red  in  color ;  it  is  rough 
and  ragged  and  is  irregularly  covered  with  purulent  exudate. 

"  The  lower  surface  of  the  specimen  consists  of  bright  yellow  fat  tissue 
through  which  is  a  delicate  tracery  of  grayish-white  fibrous  tissue.  In  the 
central  part  of  this  surface  of  the  specimen  (the  thinner  area  above 
referred  to)  there  is  an  area  (3.5  x4  centimeters)  of  firm,  dense,  grayish- 
white  glistening  elastic  fibrous  tissue.  On  section  this  fibrous  '  disc  '  is 
seen  to  be  in  places  in  continuity  with  the  base  of  the  ulcer ;  in  other 
places  it  is  connected  by  fine  and  coarse  fibrous  strands. 

"  The  margin  of  skin  surrounding  the  ulcer  is  from  i  to  3  centimeters 
in  width :  it  is  thicker  and  firmer  than  normal  skin ;  it  is  diffusely  red- 
dened with  a  deep  punctate  erythema,  except  for  numerous,  slightly 
elevated,  rounded,  whitened  areas  (.3  to  .6  centimeter  in  size)  which 
have  a  distinct  nodular,  almost  '  shotty '  feel.  On  section,  these  areas 
are  .4  to  .6  centimeter  in  thickness  ;  the  surrounding  skin  is  .2  to  .3  centi- 
meter thick.  The  bright  punctate  appearance  in  the  diffuse  erythema 
of  the  skin  surrounding  the  ulcer  is  apparently  due  to  marked  injection  of 
very  small  blood  vessels. 

"Microscopic  examination:  I.  Disc  of  fibrous  tissue,  from  deeper 
tissue  of  lower  portion  of  tissue,  forming  floor  of  ulcer. 

"  This  tissue  is  dense  fibrous  tissue  poor  in  cells,  composed  of  bundles 
which  run  in  all  directions.  There  are  numerous  small  arteries  and  veins 
and  capillaries,  all  of  which  are  surrounded  by  narrow  zones  of  lymphoid 
and  plasma  cell  infiltration.  The  amount  of  elastic  tissue  is  small,  and 
that  present  is  in  small  masses,  usually  composed  of  clumps  of  thick  fibers, 
most  abundant  in  the  neighborhood  of  the  larger  vessels. 

"II.  Section  of  nodules  or  elevated  areas  of  skin  found  at  the  periph- 
ery of  ulcer. 

"The  epidermis  for  the  greater  partis  markedly  thin.  There  are  no 
hair  follicles  or  glands  of  any  sort.  The  corium  is  composed  of  dense 
fibrous  tissue  continuous  with  the  deeper  tissues  so  that  its  normal  rela- 
tions and  appearances  are  gone.  There  are  no  papillae  so  that  the 
epidermis  lies  evenly  upon  dense  white  fibrous  tissue.  The  corium  imme- 
diately beneath  the  epidermis  in  places  stains  very  poorly.  There  is 
marked   diminution    of  collagen   fibrils   and    there  are  many   connective 


SURGICAL   TREATMENT    OF   X-RAY   CARCINOMA.         373 

tissue  cells  of  embryonic  type.  There  are  many  large  spaces  filled  with 
blood  and  lined  by  a  single  layer  of  endothelium,  which  on  one  side  may 
lie  directly  in  contact  with  the  epidermis.  The  corium  is  composed  of 
dense  fibrous  tissue  continuous  with  the  subcutaneous  tissue  so  that  there 
is  one  compact  layer  between  the  skin  and  fat  tissue.  This  fibrous  tissue 
contains  areas  with  excessive  amounts  of  elastic  tissue  resembling  the 
masses  of  elastic  tissue  found  in  the  stroma  of  carcinomata.  In  a  few 
places  there  is  a  marked  downgrowth  of  epithelium  between  dilated 
vessels.  A  few  areas  show  branching  stalks  of  epithelium  with  character- 
istic pearls  or  onion  bodies.  There  is  marked  lymphoid  and  plasma  cell 
infiltration  about  the  epithelial  downgrowths.  The  atypical  character  of 
the  epithelium,  the  presence  of  pearls  and  many  mitoses  and  the  relation- 
ship of  epithelium  to  connective  tissue  in  these  downgrowths  warrant  the 
diagnosis  of  epidermoid  carcinomata. 

"The  ulcers:  All  show  similar  appearances.  The  floor  is  usually 
covered  with  fibrin  and  pus,  underlying  which  is  granulation  tissue.  The 
epidermis  at  the  edges  shows  slight  downgrowths  which  do  not  suggest 
malignancy.  The  deep  connective  tissue  contains  areas  of  elastic  tissue 
increase  like  those  described  above.  Completely  and  partially  obliterated 
arteries  are  common  in  the  subcutaneous  fibrous  tissue.  The  obliteration 
is  caused  by  a  proliferation  of  intimal  connective  tissue.  A  few  nerve 
trunks  are  found  showing  increased  connective  tissue  and  compressed 
nerve  fibers.  The  fat  tissue  below  and  adjacent  to  the  ulcers  show 
absorption  with  organization.  The  newly-formed  tissue  contains  many 
large,  occasionally  multinucleated  and  grotesquely  shaped  cells,  which 
are  derived  from  connective  tissue  as  shown  by  the  presence  of  fibroglia 
fibrils  when  stained  by  Mallory's  methods." 

The  operation  was  followed  by.  marked  reaction,  pain,  temperature  of 
102,  rapid  pulse,  exhaustion,  and  at  the  end  of  three  or  four  days  con- 
tinuous sloughing  of  the  edges  of  the  wound,  involving  the  skin  more 
than  the  fat.  The  wound  at  first  was  dressed  with  dry  gauze,  but  this 
was  soon  replaced,  on  account  of  pain,  by  ichthyol  lanolin  ointment  on 
bandage  cloth.  By  March  15  necrosis  stopped  temporarily,  and  granu- 
lation was  beginning.  The  constitutional  symptoms  were  distinctly 
better,  though  fever  in  the  afternoon  still  persisted.  On  March  20,  the 
condition  was  as  follows  :  the  edges  of  the  skin,  in  the  right  groin,  had 
ceased  sloughing  and  granulation  was  fairly  well  established.  On  the 
left,  however,  necrosis  still  proceeded  involving  only  the  skin,  whereas  the 
fat  was  granulating  healthily.  There  are  new  areas  of  necrosis,  varying 
in  size  from  a  dime  to  a  split  pea  in  the  thickened  skin,  near  the  margin 
of  the  wound.  There  is  not  much  discharge,  no  enlargement  of  the 
glands  in  either  groin,  and  the  general  condition  of  the  patient  is  slowly 
but  steadily  improving.  Her  chief  complaint  is  of  pain  in  the  right  loin, 
the  lightest  contact  over  the  old  scar  causing  extreme  shooting  pains. 
This  cicatrix  is  covered  with  an  adherent  diphtheritic  membrane  which  is 
extremely  tough.  If  a  portion  of  it  be  peeled  off,  bleeding  is  free.  Cult- 
ures were  made  and  sent  to  Dr.  Wolbach,  and  he  reported  that  bacilli, 


374  PORTER. 

morphologically  similar  to  diphtheria,  were  present;  inoculation  however 
showed  that  they  were  inactive. 

April  25  :  For  the  past  two  weeks  the  wound  has  been  granulating 
healthily  throughout  its  greater  part.  The  central  zone  which  comprised 
the  old  scar  is  behaving  in  a  most  unique  fashion.  The  area,  which  a 
month  ago  was  covered  by  a  diphtheritic  membrane,  is  now  changed  to  a 
smooth,  glistening  surface,  which  bleeds  on  the  slightest  touch.  From 
the  periphery,  granulation  is  slowly  stealing  in.  The  skin  in  the  right 
pubic  region  is  healing  soundly,  and  the  epithelium  is  growing  normally 
over  the  granulations.  Just  above  the  right  iliac  spine  is  an  irregular  dirty 
fibrin-covered  ulcer,  about  the  size  of  the  end  of  the  thumb.  The  deeper 
layers  of  the  skin  are  necrotic.  In  the  central  portion,  above  the  umbil- 
icus are  a  number  of  similar  radiating  ulcerations.  There  are  some  lymph- 
angitis about  the  wound.  The  undermining  at  the  left-hand  side  of  the 
wound  is  less  marked.  From  her  morning  headaches,  nervous  feelings, 
and  poor  pulse,  it  would  seem  as  if  there  was  continuous,  slight  infection 
from  the  wound,  though  the  temperature  is  now  almost  normal.  During 
the  summer  she  lived  in  a  tent,  the  wound  being  dressed  twice  daily. 
Granulation  was  slow  and  epithelium  once  formed  frequently  broke  down, 
but  over  the  pubic  region,  and  in  the  right  groin,  epidermization  con- 
tinued satisfactorily  but  slowly  and  gradually  the  ulcerations  starting  in 
the  skin  spread,  the  size  of  the  wound  was  continually  increasing,  by  their 
confluence,  in  all  directions.  In  view,  however,  of  her  marked  prostra- 
tion, after  her  iirst  operation,  it  seemed  better  to  allow  the  tissues  to 
slough  rather  than  to  remove  them.  During  September  her  general  con- 
dition improved  very  markedly,  and  with  this  the  central  granulating 
wound  took  on  a  more  normal  appearance.  On  September  28,  I  decided 
upon  another  operation,  at  which,  under  ether,  I  removed  the  remaining 
skin  of  the  anterior  abdominal  wall,  as  far  out  on  both  sides  as  the  ante- 
rior superior  spines  and  upwards  to  a  level  of  four  inches  above  the  umbil- 
icus. At  this  operation,  I  only  removed  the  skin,  leaving  behind  as  much 
as  possible  of  the  fat  tissue.  The  wound  was  dressed  with  protective. 
Reaction  was  well  marked  but  was  less  severe  than  after  the  previous 
operation,  and  the  temperature  became  normal  in  ten  days. 

By  Dec.  5,  1908,  the  patient  had  gained  in  general  strength  and  color, 
and  was  walking  about.  Healing  has  taken  place  rapidly  from  the  edges, 
and  with  the  exception  of  some  painful  ulcerations  in  the  remaining  skin 
of  the  left  groin  the  whole  wound  is  granulating  for  the  first  time,  in  a 
perfectly  normal  manner.  On  this  date,  three  long,  narrow  Thiersch 
grafts  were  taken  from  the  arm  of  a  friend,  cut  into  fourteen  pieces  about 
three-quarters  of  an  inch  square,  and  scattered  over  the  granulating  sur- 
face. They  were  held  in  position  by  broad  strips  of  cr6pe  lisse,  covered 
with  protective  tissue.  After  twenty-four  hours,  salt  solution  fomenta- 
tions were  applied  frequently,  and  at  the  end  of  ten  days  twelve  had 
healed  soundly  in  position,  thus  greatly  diminishing  the  denuded  area. 
Dec.  24,  1908.  All  of  the  grafts  have  grown  vigorously  during  the 
past  week.     It  seems  as  if  no  further  grafting  would  be  necessary,   as 


SURGICAL   TREATMENT   OF   X-RAY   CARCINOMA.         375 

three-fourths  of  the  huge  granulating  wound  is  now  covered  with  appar- 
ently healthy  epithelium.  There  is  in  the  left  groin,  outside  the  edge  of 
the  wound,  an  irregular,  unhealthy  ulceration,  which  is  extremely  sore  and 
tender.     This  must  be  grafted  at  a  later  period. 

Feb.  24,  1909.  After  three  or  four  weeks  all  of  the  grafts  taken  from 
her  friend  were  raised  by  blisters  and  slowly  disappeared.  Two  weeks 
ago  the  left  end  of  the  wound  was  grafted  with  snips  from  her  thigh ;  of 
nine,  eight  took  and  have  grown  well.  In  view,  however,  of  the  slow 
progress  it  seemed  to  me  best  to  operate  this  morning,  February  23. 
Accordingly,  under  gas  and  ether,  the  wound  was  thoroughly  cleaned 
with  green  soap  and  water,  and  the  granulations  vigorously  scrubbed  with 
salt  solution,  followed  by  a  copious  saline  irrigation.  Moderately  thin 
Thiersch  grafts  were  removed  from  the  right  thigh,  and  the  whole  wound 
covered.  One  could  not  but  be  surprised  by  the  copious  serous  discharge 
from  the  whole  granulating  surface.  I  have  never  seen  anything  like  it. 
Whether  this  was  due  to  some  peculiar  condition,  or  possibly  to  the  irrita- 
tion of  the  green  soap,  I  do  not  know.  The  grafts  were  covered  with 
protective,  gauze  was  then  placed  carefully  over  the  uneven  surfaces,  and 
held  in  place  by  adhesive  plaster.  The  thigh  was  covered  with  protective 
and  bandage.  A  snug  swathe  was  then  evenly  fitted  over  the  whole 
abdomen,  making  all  possible  pressure. 

April  I,  1909.  With  a  few  exceptions,  all  of  the  Thiersch  grafts  took, 
and,  with  their  continued  growth,  at  present  the  huge  wound  is  continuously 
covered  with  sound,  thick,  and  somewhat  movable  skin,  except  for  an 
area  on  the  right  hand  upper  margin,  2x3  centimeters.  There  is  no 
tenderness  in  the  scar,  and  no  pain.  Patient  has  been  up  and  about  for 
three  weeks,  having  been  in  the  hospital  thirteen  months.  Owing  to  con- 
tinued flexion  of  the  thighs  there  is  some  subluxation  of  both  knee 
joints,  and  she  walks  clumsily  and  somewhat  in  a  stooping  manner,  owing 
to  the  contraction  of  the  anterior  muscles  of  the  body.  There  is  no 
evidence  of  recurrence  of  the  sarcoma.    Her  general  condition  is  excellent. 

Summary :  This  patient,  after  unsuccessful  treatment  of  ten  months 
with  Coley's  serum  for  a  fibrosarcoma  of  the  abdominal  wall,  was  entirely 
cured  of  this  condition  by  one  hundred  and  thirty-six  X-ray  treatments, 
covering  a  period  of  two  years  and  three  months.  She  was  well  for  four 
years,  except  for  some  thickening  of  the  skin  and  telangiectases,  when 
severer  and  characteristic  X-ray  lesions  developed,  not  only  in  the  scar 
of  the  shrunken  tumor,  but  in  the  skin  over  the  whole  anterior  abdomen. 
In  addition  to  the  ulcerations  of  the  skin,  which  not  only  refused  to  heal 
under  all  treatment,  but  steadily  increased  in  depth  and  area,  there  were 
numerous  papules  of  undoubted  epidermoid  cancer.  At  the  first  opera- 
tion the  ulcerated  areas  of  the  lower  abdomen  were  thoroughly  excised 
with  wide  margins,  down  to  the  scar  of  the  tumor  and  the  anterior  aponeu- 
roses. The  operation  was  followed  by  marked  infection,  which  was 
questionably  diphtheritic.  The  wound  was  extremely  sluggish  and  granu- 
lations very  slowly  formed,  covered  by  unhealthy  fibrin.  General  con- 
dition   poor.     After    months    of    convalescence,    granulation    gradually 


376  PORTER. 

established,  and  epidermization  slowly  took  place  from  the  pubic  and 
inguinal  regions,  but  the  thickened  skin  ulcerated  upward  and  laterally, 
with  great  pain  and  some  fever.  Six  months  after  the  first  operation  I 
decided  under  ether  to  remove  the  remaining  thickened  skin  of  the 
anterior  abdominal  wall  for  a  distance  of  four  inches  above  the  umbilicus, 
and  laterally  to  a  level  with  the  anterior  superior  spines.  The  skin  and 
upper  half  of  the  subcutaneous  fat  alone  was  removed.  The  wound  was 
dressed  with  protective.  After  two  months,  the  wound  at  that  time  granu- 
lating healthily,  a  number  of  Thiersch  grafts  were  removed  from  the  arm 
of  a  friend  and  applied  over  the  large  surface.  In  three  weeks,  healing 
was  almost  complete,  but  in  two  more  the  apparently  healthy  grafts  began 
to  blister  and  come  away.  In  three  weeks  more,  patient  was  etherized 
and  grafts  from  her  own  thigh  placed  in  position.  These  at  the  present 
time,  thirteen  months  after  the  first  operation,  have  grown  soundly  and 
the  whole  wound  is  healed.  This  case  should  serve  as  a  warning  not  to 
use  Thiersch  grafts  from  other  people,  unless  the  condition  of  the  patient 
contraindicates  ether. 

Case  IX.  —  M.  K.  K.  (physician);  40  years;  X-ray  operator,  Phila- 
delphia. Began  work  in  1899.  In  1901,  hands  showed  usual  early 
lesions ;  telangiectases,  ribbing  of  the  nails  and  thickened  fissured  skin. 
In  1903  the  superficial  ulcerations  and  keratoses  shown  in  the  photo- 
graphs, involving  the  lower  parts  of  the  hands  and  fingers.     By  January, 

1908,  there  was  general  improvement  of  the  dorsum  of  the  hands  and 
fingers  of  the  right  hand,  but  an  extensive  and  suspicious  keratosis  at  the 
base  of  the  fourth  finger.  For  two  years  there  has  been  ulceration  of 
the  two  terminal  phalanges  of  the  middle  finger  of  the  left  hand,  and  for 
eighteen  months  a  similar  condition  over  the  first  phalanx  and  distal 
joint  of  the  fourth  finger.  By  December,  1908,  the  large  keratosis  on  the 
right  hand,  under  treatment,  has  almost  disappeared,  but  the  ulcerations 
on  the  end  of  the  middle  finger  of  the  left  hand  were  typically  malignant. 
The  ulcerations  and  a  keratosis  on  the  ring  finger  became  infected,  and 
an  exuberant  growth  appeared  increasing  rapidly  in  size.     On   April  4, 

1909,  the  middle  finger  was  amputated  at  the  end  of  the  first  phalanx, 
and  the  ring  finger  at  the  knuckle.  There  were  no  glands  in  the  axilla. 
(Pathological  diagnosis:  epidermoid  carcinoma;  Plate  XXXV.,  Figs. 
4,  5,  6.) 

Case  X.  —  M.  N. ;  35  years;  Swede.  Personal  communication  from 
Dr.  A.  D.  Bevan  of  Chicago.  In  April,  1902,  had  abscess  of  obscure 
nature  in  left  lower  quadrant  of  abdomen.  This  was  opened  and  found 
to  be  fecal  and  drained.  A  fecal  fistua  resulted,  which  was  closed  at 
operation  August,  1902.  He  returned  again  October,  1902,  with  symp- 
toms of  intestinal  obstruction  and  an  exploratory  laparotomy  was  per- 
formed and  a  tumor-like  mass  found  in  the  descending  colon.  The 
operation  was  purely  exploratory.  December,  1902,  he  again  had  symp- 
toms of  obstruction ;  another  operation  was  performed ;  some  adhesions 


SURGICAL   TREATMENT   OF   X-RAY   CARCINOMA.         377 

between  the  small  intestine  and  descending  colon  separated,  and  a 
Meckel's  diverticulum  was  found  and  removed.  This  apparently  had 
nothing  to  do  with  his  illness.  The  tumor-like  mass  in  the  colon  was  of 
uncertain  diagnosis ;  we  regarded  it  as  either  carcinoma,  syphilis,  or 
tuberculosis.  He  was  given  antispecific  treatment  and  was  given  a  large 
number  of  X-ray  exposures  over  the  mass.  This  resulted  in  rather  an 
extensive  X-ray  burn,  which  healed  slowly.  The  swelling  in  the  abdomen 
disappeared  and  the  man  made  an  apparently  complete  recovery. 

October,  1908,  he  returned  to  the  hospital  with  several  irregular  ulcers 
in  the  scar  of  the  X-ray  burn.  It  was  thought  that  they  were  suspicious 
of  carcinoma  and  a  large  area  about  6x6  inches  containing  the  scar  of 
the  old  X-ray  burn  and  these  ulcers  were  dissected  off,  and  the  surface 
covered  with  skin  grafts.  The  microscopical  sections  from  the  margin  of 
the  ulcers  show  a  suspicion  of  beginning  carcinoma.  There  is  prolifera- 
tion of  the  epithelial  cells  with  processes  extending  a  moderate  depth  in 
the  subcutaneous  tissue,  in  several  portions  of  the  section,  but  only  at 
these  points  is  the  basement  membrane  broken.  There  is  some  round 
cell  infiltration ;  nowhere  is  there  a  separate  island  of  epithelial  cells  or 
epithelial  pearls.  From  the  microscopical  section  I  am  inclined  to  regard 
it  as  a  beginning  epithelioma. 

Summa?y :  Large  number  of  X-ray  exposures  for  abdominal  tumor ; 
extensive  burn  which  healed  slowly.  Latent  period  at  least  five  years, 
when  several  irregular  ulcers  developed  in  the  scar.  A  large  area  6x6 
inches  dissected  off  with  successful  skin  grafting.  Pathological  report : 
beginning  epithelioma. 

Case  XI.  —  Personal,  E.  W.  C. ;  aged  37  years ;  admitted  to  the 
Massachusetts  General  Hospital  Sept.  3,  1907,  with  the  following  history : 
Shortly  after  beginning  work  with  the  X-rays,  ten  years  ago,  patient 
noticed  desquamation  and  ulcerative  areas  appearing  on  the  dorsum  and 
knuckles  of  left  hand.  He  also  developed  telangiectases  of  left  thigh  and 
lower  abdomen.  Although  he  has  long  since  ceased  to  expose  himself, 
the  parts  have  continued  to  ulcerate,  until  some  of  them  have  taken  on  a 
more  deep-seated  epitheliomatous  character.  He  has  tried  all  sorts  of 
washes  and  ointments,  exposure  to  sunlight,  arc  light,  with  and  without 
screens,  and  the  so-called  luecodescent  light.  In  his  case,  all  of  these 
agents  were  harmful ;  the  relief  reported  by  some,  he  explained,  as  due 
entirely  to  the  heating  effect,  for  the  pain,  which  prevented  sleep,  would 
often  yield  to  treatment  for  fifteen  or  twenty  minutes,  with  an  electric 
heating  pad. 

Examination  of  left  hand  shows  the  usual  telangiectases,  atrophy  of  the 
skin,  with  numerous  keratoses  and  papules,  and  several  ulcerated  areas ; 
two  in  particular  appearing  most  suspicious  —  one  at  the  base  of  the  first 
finger,  and  another  in  the  cleft  between  it  and  the  thumb.  There  were 
superficial  ulcerations  with  keratoses  over  the  interphalangeal  knuckles  of 
the  first  two  fingers,  and  another  rather  extensive  keratosis  at  the  base  of 
the  ring  finger. 


378  PORTER. 

Under  ether,  Sept.  4,  1907,  all  of  these  areas  were  excised,  the  suspi- 
cious ones  down  to  the  subcutaneous  tissues ;  the  others  well  into  the 
corium.  Skin  grafts  of  moderate  thickness  were  applied  to  the  wound, 
after  bleeding  had  ceased.  Protective  tissue,  just  outside  the  periphery  of 
the  grafts,  with  firm  pressure  applied  by  a  gauze  roller,  the  hand  having 
previously  been  immobilized  upon  a  well-padded  splint.  On  the  5th, 
rubber  tissue  removed,  and  grafts  exposed  to  air,  covered  with  ointment. 
On  the  7th,  grafts  looked  finely.  On  the  8th,  grafts  were  all  looking  well, 
except  one  over  the  fourth  metacarpo-phalangeal  joint,  which  is  a  little 
white  in  the  center,  where  a  small  necrotic  area  has  developed.  On  the 
9th,  all  grafts  had  taken,  except  the  one  previously  mentioned  over  the 
knuckle  of  the  ring  finger.  Discharged  on  September  12,  eight  days  after 
operation. 

Pathological  examination  showed  that  ulceration  at  the  base  of  the  fore- 
finger was  undoubtedly  epithelioma.  In  two  other  places,  a  precancerous 
condition  was  present ;  the  tissues  from  other  parts  showed  superficial 
ulcerations  or  keratoses. 

Quotation  from  letter  dated  Sept.  15,  1908  :  "For  your  records,  I  have 
to  report  that  all  the  grafts  grew  successfully,  and  most  of  them  have  con- 
tracted much  more  than  I  expected.  They  are  all  in  splendid  condition, 
except  that  there  is  a  tendency  to  the  formation  of  keratoses  at  some  of  the 
margins.  It  seems  to  me  that  this  condition,  so  common  in  all  X-ray 
hands,  nearly  always  starts  from  a  small  abrasion,  and  that  the  trauma  at 
the  margin  of  the  incision  for  the  skin  graft  is  just  the  sort  of  injury 
which  has  produced  this  kind  of  growth.  I  have  been  able  to  improve  the 
condition  very  much  by  having  these  spots  treated  with  liquid  air,  after 
which  there  is  no  tendency  toward  recurrence.  There  are  no  signs  of 
metastatic  involvement  of  the  epitrochlear  or  axillary  glands." 

SiDiimary  ;  Characteristic  X-ray  hands.  For  several  years,  intermittent 
healing  and  ulceration ;  finally  persistent  ulceration  in  spite  of  treatment 
by  various  forms  of  light,  in  addition  to  the  usual  treatment.  Eight 
excisions ;  all  grafts  successful.  One  undoubted  carcinoma ;  two  pre- 
cancerous lesions.  All  keratoses  which  formed  at  margins  of  graft  suc- 
cessfully treated  with  liquid  air.  No  return  of  ulcerations  or  of  disease. 
Satisfactory  result. 

Case  XII.  —  S.  L.  (physician),  New  York.  Personal  communication 
in  regard  to  his  own  case.  "  Frequent  excisions  of  epitheliomatous  areas, 
which  broke  down  from  time  to  time,  has  reduced  them  to  a  definite 
number;  five  on  my  left  hand  of  very  small  size.  Of  course  I  have  abso- 
lutely given  up  the  use  of  the  X-ray,  and  have  even  had  my  machine 
removed  from  the  office.  I  still  find  that  the  left  hand  resists  chemicals 
very  badly.  Too  strong  or  too  frequent  use  of  bichlorid  will  give  me  an 
eczematous  condition,  which  immediately  lights  up  the  spots  from  which 
the  epitheliomata  have  been  removed." 

Case  XIII.  —  C.  L.  L.   (physician).     Several  years  ago  developed  an 


SURGICAL   TREATMENT    OF   X-RAY    CARCINOMA.         379 

epithelioma  of  his  forefinger,  and  fearing  excision  or  even  amputation,  lest 
metastases  result,  applied  the  X-ray  very  vigorously,  with  the  intention  of 
destroying  all  malignant  cells  before  operation.  He  produced  a  slough 
which  extended  to  the  bone,  after  which  the  finger  was  amputated  and 
healed  by  primary  union.  There  are  a  few  suspicious  areas  over  the 
fingers  of  the  same  hand  ;  no  glandular  involvement. 

Case  XIV. — Mr.  S.,  New  York,  radiographer.  Amputation  of  one 
finger  for  epithelioma  developing  in  an  X-ray  lesion.     Now  well. 

Case  XV.—  Personal.  Wolbach,  Case  V.  Plate  XXXVI.,  Figs.  7  to 
II  (inclusive).  F.  H.  S.  Patient  sent  to  me  by  Dr.  Percy  Brown. 
First  used  X-ray  apparatus  in  the  spring  of  1897;  static  machine. 
Received  acute  dermatitis  on  back  of  left  hand,  which  after  healing 
showed  characteristic  pigmentation.  He  has  had  a  few  attacks  of  acute 
processes  since  then,  but  not  until  three  years  ago  did  an  ulcer  form  on 
the  back  of  the  left  hand  between  the  knuckles  of  the  first  and  second 
fingers.  This  healed  up  several  times  and  broke  down  again.  Over  the 
backs  of  the  hands  in  various  places  keratoses  have  formed  which  became 
black  and  then  spontaneously  fell  off.  Sometimes  has  scraped  them  off 
with  pumice  stone.  Except  for  the  inconvenience  of  dressing  the  ulcera- 
tion he  has  had  practically  no  pain  in  his  hand  since  the  original  derma- 
titis. For  many  years  he  has  noticed  that  the  skin  on  the  front  of  his 
chest  has  become  thickened  ;  here  and  there  are  somewhat  more  indurated 
spots;  the  whole  chest  is  covered  with  the  characteristic  venules.  For  a 
number  of  months  he  has  noticed  that  the  pores  of  the  tip  of  his  nose  have 
filled  up,  occasionally  discharging  sebaceous  matter.  For  two  months 
and  a  half  he  has  noticed  a  warty  growth  on  tip  of  nose  about  the  size  of  a 
pea. 

Examination :  On  the  tip  of  the  nose  is  a  warty  growth  on  which  a  scab 
has  formed  of  the  size  before  mentioned.  This  discharges  some  serum, 
no  pus ;  is  not  sore.  The  chest  presents  the  characteristic  appearance  of 
chronic  X-ray  dermatitis  with  telangiectases  and  some  pigmentation. 
There  is  thickening  of  the  skin  in  plaques,  but  no  ulceration.  The  skin 
of  the  back  of  the  left  hand  is  thickened  in  some  places,  especially  over 
the  joints  where  it  is  atrophic  and  cracked.  As  shown  in  the  photograph, 
there  are  about  half  a  dozen  keratoses,  the  skin  about  them  being 
thickened  to  twice  normal.  At  the  cleft  between  the  first  and  second 
fingers  is  a  well-marked  induration  with  a  keratosis  growing  on  the  distal 
part.  Above  this  are  three  open  ulcerations,  the  distal  one  having 
slightly  raised  indurated  edges.  The  proximal  one  is  flat,  non-indurated, 
appearing  like  smooth  granulation  tissue.  Diagnosis  of  the  distal  ulcera- 
tion probably  beginning  epithelioma  ;  of  the  proximal  one,  simple  ulcer. 

Operation  under  ether  March  29,  1908.  Ulcerated  area  on  back  of 
hand  carefully  excised  with  broad  margin  down  to  underlying  veins,  fat 
and  tendon  of  middle  finger.  Edge  of  thickened  skin  bevelled.  Several 
Indurated  areas  and  keratoses  were  either  excised  or  shaved  down  to  the 


380  PORTER. 

deep  skin.  All  of  the  raw  places  were  skin  grafted  from  the  left  arm. 
The  growth  on  the  tip  of  the  nose  was  shaved  off  deeply.  All  of  the 
wounds  were  covered  with  protective  and  the  hand  firmly  bandaged  on  a 
splint  and  elevated.     No  dressing  applied  to  nose. 

For  purposes  of  microscopic  examination,  an  indurated  superficial 
ulcerated  papule  in  the  cardiac  area  of  the  chest  was  removed  by  an 
elliptical  incision,  and  the  skin  approximated  with  silkworm  gut  sutures. 

Convalescence :  the  usual  protective  dressing  remained  in  position  for 
twenty-four  hours,  then  ointment  and  cage.  Patient  discharged  in  a 
week. 

Pathological  examination  by  Dr.  Wolbach. 

1.  Keratosis  from  nose.     (Plate  XXXVI.,  Fig.  ii.) 

The  epidermis  is  greatly  thickened  and  irregular  and  the  horny  layer  is 
heaped  up,  forming  a  thick  layer  of  keratinized  cells.  The  cells  of  the 
stratum  germinativum  are  large,  vesicular,  and  present  mitoses.  In  some 
by  high  power  fields  as  many  as  ten  mitoses  are  found.  The  processes 
extending  into  the  corium  for  the  most  part  present  an  orderly  arranged 
basal  layer  except  in  a  few  places  where  the  epidermis  is  infiltrated  with 
lymphoid  and  plasma  cells.  The  corium  immediately  beneath  the 
epidermis  is  thinned  in  places.  Some  of  the  smaller  vessels  are  filled 
with  polynuclear  leucocytes.  There  is  everywhere  extensive  infiltration 
with  lymphoid  and  plasma  cells  beneath  the  epidermis.  The  epidermis 
on  either  side  of  the  keratosis  is  practically  normal. 

The  most  striking  feature  of  this  tissue  is  the  extraordinary  number  of 
mitotic  cells  in  the  epithelial  processes  and  the  change  in  the  character  of 
the  cells  from  the  compact,  basic-staining  appearance  of  the  normal 
epidermal  cells  to  the  large  vesicular  neutral-staining  cells  found  in  the 
processes  beneath  the  keratosis. 

2.  Large  ulcer  from  hand.     (Plate  XXXVI.,  Fig.  8.) 

The  ulcerated  surface  is  practically  the  exposed  surface  of  a  vascular 
new  growth  of  epithelium,  atypical  in  type  and  containing  many  whorls  of 
keratinized  cells.  This  tissue  is  microscopically  a  typical  epidermoid 
carcinoma  and  there  is  definite  evidence  of  invasion  of  the  corium.  The 
epidermis  on  each  side  of  the  central  mass  is  irregularly  thickened  in 
places  and  thinned  in  others.  The  corium  immediately  beneath  the 
epidermis  is  rarefied.  A  few  arteries  show  thickened  walls.  No  sweat 
glands  or  hair  follicles  found  in  the  sections. 

3.  Keratosis  of  hand  between  index  and  middle  fingers. 

The  same  general  picture  is  found  here  as  in  the  tissue  removed  from 
the  nose.  The  rarefication  of  the  corium  beneath  the  surrounding 
approximately  normal  epidermis  is  more  striking  than  in  the  case  of  the 
nose.  There  is  less  infiltration  beneath  the  keratosis,  and  the  epithelium 
shows  comparatively  few  mitoses.     No  positive  evidence  of  malignancy. 

4.  Tissue  from  the  chest.     (Plate  XXXVI.,  Fig.  10.) 

Consists  of  a  semicircular  piece  of  tissue  the  convex  border  of  which  is 
covered  by  epidermis.  The  central  portion  of  the  tissue  is  very  similar  to 
that  from  the  ulcer  of  the  hand  in  that  we  have  a  new  growth  of  epidermis 


SURGICAL   TREATMENT   OF   X-RAY   CARCINOMA.         38 1 

supplied  with  many  blood  vessels  and  having  no  definite  epidermal  cover- 
ing. The  projecting  stalks  of  the  central  mass  contain  many  whorls  of 
keratinized  cells,  and  the  relationship  to  the  connective  tissue  of  the 
corium  leaves  no  doubt  that  the  tissue  is  that  of  a  new  growth,  epider- 
moid carcinoma  in  type.  The  corium  beneath  the  surrounding  epidermis 
shows  the  same  rarefication  noted  in  other  cases. 

General  Note :  A  description  of  the  new  growths  from  the  hand  and 
from  the  chest  hardly  seems  necessary.  In  both  locations  the  picture  is 
that  of  typical  epidermoid  carcinoma.  Mitoses  are  numerous  and  the 
masses  of  epithelium  enclose  remnants  of  elastic  fibers  and  collagenous 
connective  tissue.  In  the  corium,  immediately  beneath  the  new  growth,  . 
there  is  more  increase  in  elastic  tissue,  otherwise  the  changes  in  the  deeper 
tissue  are  similar  to  those  noted  in  the  cases  of  H.  and  S. 

April  22,  1908.  Patient  visited  me  the  day  before  yesterday.  All  of 
the  skin  grafts  have  healed  and  now  show  the  usual  increase  in  vascularity 
and  are  raised  above  the  surrounding  skin.  The  large  graft  on  the  back 
of  the  hand  shows  a  slightly  hypertrophic  condition,  but  is  beginning  to  be 
movable  on  the  underlying  tissues.  Several  areas  of  keratoses  are  slowly 
reforming. 

May  30,  1908.  The  pathological  report  that  the  papule  excised  from 
the  chest  was  carcinoma  came  as  a  complete  surprise.  This  fact  was 
explained  to  the  patient,  and  on  May  29,  under  cocaine,  the  scar  of  the 
former  operation  was  excised  with  a  wide  margin  down  to  the  subcu- 
taneous fat;  wound  closed  with  sutures. 

December,  1908.  Present  condition:  the  nose  is  slightly  flattened  at 
the  tip  and  shows  a  slight  scar.  Grafted  area  upon  the  hand  shows  no 
evidence  of  recurrence  of  the  carcinoma,  and  is  quite  freely  movable  upon 
the  underlying  structures.  There  are  several  cracks  and  fissures,  as  well 
as  keratoses  on  the  various  parts  of  the  hand,  but  nothing  suggesting  epi- 
thelioma. There  is  no  return  of  the  cancer  at  the  site  of  the  excision  over 
the  breast. 

Su7n)nary :  Early  acute  dermatitis  in  1897;  innumerable  exposures  of 
chest  for  fluoroscopic  examination  of  heart.  Characteristic  lesions  of 
chest  and  left  hand  ;  ulceration  of  hand  persisted  for  three  years  ;  no  pain. 
Operation  :  excision  of  keratosis  on  tip  of  nose,  of  ulceration  of  hand  and 
keratoses  ;  successful  skin  graft.  Excision  of  papule  on  chest  for  examina- 
tion, which  proved  to  be  undoubted  epithelioma.  Prognosis  doubtful,  as 
the  remains  of  the  indurated  tissues  of  chest  may  develop  carcinoma. 
Very  satisfactory  graft. 

Case  XVI.  —  G.  W.  D. ;  32  years  ;  radiographer  and  salesman.  Patient 
of  Dr.  F.  E.  Pinkham,  Providence,  R.I.  Patient  began  work  in  1896. 
Had  amputation  of  ring  finger  of  left  hand  at  the  Worcester  City  Hospital 
in  1905,  on  account  of  ulceration  and  exuberant  growth  which  had  been 
microscopically  examined  and  pronounced  to  be  an  epithelioma.  He 
entered  the  Massachusetts  General  Hospital  April  7,  1908,  having  noticed, 
six  weeks  ago,  a  hard  lump  in  the  axilla  which,  though  slightly  tender, 


382  PORTER. 

was  not  painful.     In  the  past  three  weeks  there  had  been  rapid  growth  of 
this  tumor.     No  loss  of  weight. 

Examination  of  left  hand :  ring  finger  amputated  at  the  metacarpo 
phalangeal  joint.  On  the  dorsum  of  back  of  hand  are  several  small  kera- 
totic  areas  which  have  been  present  since  1899.  Skin  of  dorsum  of  hand 
is  hard  and  indurated.  No  enlargement  of  left  epitrochlear  gland.  In 
the  left  axilla  is  a  tumor  about  the  size  of  a  hen's  egg,  which  is  slightly 
elastic  and  tender,  and  more  or  less  fixed  to  the  surrounding  tissues.  No 
palpable  glands  above  clavicle. 

Operation,  April  7,  1908.  Incision  made  through  center  of  axilla  over 
the  mass,  parallel  to  the  lower  border  of  the  pectoralis  major  muscle. 
Skin  dissected  back ;  axillary  fascia  opened ;  gland  found  to  be  very  hard, 
possibly  slightly  fluctuating  in  the  center.  Incision  made  into  it,  speci- 
men given  to  Drs.  Kidner  and  Wright  for  examination.  Frozen  section 
showed  undoubted  epithelioma.  The  center  of  the  gland  was  softened 
and  about  a  teaspoonful  of  pus  or  epithelial  debris  escaped.  An  incision 
was  then  made  upward  from  the  other,  at  right  angles  to  the  collar  bone. 
The  pectoralis  major  muscle  was  divided  and  retracted,  and  the  pectoralis 
minor  divided  at  its  insertion  into  the  coracoid  process.  By  blunt  dis- 
section the  fascia  covering  all  of  the  muscles  forming  the  axillary  triangle 
was  removed  with  the  inner  portion  of  the  pectoralis  major,  minor,  and 
axillary  third  of  the  latissimus  dorsi,  and  some  of  the  subscapularis  ;  bleed- 
ing was  quite  profuse.  The  long  thoracic  nerve  was  preserved,  but  some 
of  the  branches  of  the  subscapular  and  the  latissimus  dorsi  were  cut.  A 
part  of  the  axillary  vein  in  contact  with  the  gland  was  resected  for  a  dis- 
tance of  two  inches,  but  the  collateral  branches  of  the  brachial  veins, 
entering  above,  carried  on  the  circulation  adequately.  With  the  arm 
flexed  and  brought  forward,  the  nerves,  axillary  artery  and  vein  were 
held  forward  with  retractors  and  with  great  care,  the  whole  mass  of  gland- 
bearing  fat  was  removed  well  above  the  clavicle.  It  was  obvious  that  in 
order  to  get  good  motion  in  the  arm,  a  plastic  would  be  necessary.  The 
sternal  portion  of  the  pectoralis  major  muscle  was  therefore  freed  from  its 
attachment,  and  brought  downward  over  the  axillary  vessels  and  sutured 
to  the  insertion  of  the  muscle.  A  "U"  shaped  flap  of  skin  was  left 
attached  to  it,  and  utilized  to  close  in  the  axillary  opening. 

Convalescence :  Some  infection  occurred  from  the  pus  in  the  broken- 
down  gland,  accompanied  by  fever  for  several  days.  Several  stitches 
were  removed  and  a  portion  of  the  pectoral  muscle  sloughed,  but  patient 
was  discharged  with  a  granulating  wound  May  4,  twenty-five  days  after 
operation. 

Letter  dated  Dec.  7,  1908  :  "  I  thank  you  very  much  for  your  enquiry, 
and  am  greatly  pleased  to  report  that  I  am  enjoying  excellent  health. 
After  leaving  the  hospital,  the  wound  granulated  very  nicely  and  closed 
up  beautifully  within  three  weeks.  I  have  now  a  fairly  good  use  of  the 
arm." 

Summary:  X-ray  work  begun  in  1896;  ring  finger  aniputated  in  1905 
for  an  epithelioma  of  over  a  year's  duration.     Patient  well  until  February 


SURGICAL   TREATMENT    OF    X-RAY    CARCINOMA.         383 

1908  (three  years)  when  malignant  disease  appeared  in  the  axillary  glands  ; 
epitrochlear  not  involved.  Very  radical  dissection  of  axilla ;  some  infec- 
tion of  wound.  Sound  healing  in  six  weeks;  good  use  of  arm.  At 
present  well. 

Pathological  report  by  Dr.  Wolbach.  "  Microscopic  description : 
methylene  blue  and  eosin ;  Mallory's  connective  tissue  stain,  phospho- 
tungstic-hematein  stain.  Paraffine  sections.  Tissue  consists  of  large 
lymph  node  infiltrated  with  new  growth  consisting  of  anastomosing 
stalks  of  epithelial  cells  containing  many  whorls  of  cornified  cells.  The 
whole  is  supported  by  a  fairly  dense  connective  tissue  reticulum.  The 
picture  is  that  of  typical  rapidly-growing  epidermoid  carcinoma.  Mitoses 
are  extremely  numerous." 

Case  XVII.  — Personal.  (Plate  XXXVIII.,  Figs.  22  and  23  )  H.  G. ; 
48  years.  Consulted  me  first  in  January,  1908.  He  had  been  working 
since  the  very  beginning  in  the  manufacture  of  X-ray  tubes.  The  first 
indication  of  any  trouble  appeared  in  the  shape  of  a  red,  itching  rash,  of 
which  he  took  very  little  notice,  supposing  it  to  be  caused  by  acid  fumes. 
This  condition  was  succeeded,  the  latter  part  of  1898,  by  the  appearance 
of  a  number  of  callosities  on  the  back  of  the  hand,  which  about  the 
spring  of  1899  had  changed  into  warty  growths,  which  he  tried  to  remove 
by  pulling  them  off".  The  removal  was  attended  by  severe  pain,  and  free 
bleeding,  and  seemed  to  cause  them  to  increase  in  size  and  multiply. 
These  warts  and  other  scaly  areas  were  removed  frequently  by  means  of  a 
live  cautery,  only  to  reappear  in  increased  size.  His  physician  used 
almost  every  known  salve  but  the  only  result  was  to  allay  the  pain  some- 
what. "  No  pen  can  describe  the  sensitiveness  or  the  pain  of  these  burns." 
"  One  peculiarity  of  my  case  is  that  from  the  frequent  examination  of  my 
body  with  the  fluoroscope  by  hundreds  of  doctors,  the  skin  of  my  chest 
became  black  and  hard,  like  parchment,  giving  me,  however,  no  incon- 
venience and  never  becoming  sore ;  in  less  than  a  year,  this  blackened 
skin  all  came  off"  in  one  piece,  leaving  the  chest  clean,  without  a  scar,  but 
of  course  removing  all  hair."  For  seven  years,  then,  there  has  been 
ulceration,  induration,  and  keratosis  over  an  area  about  3  x  it  inches  on 
the  back  of  the  left  hand.  This  had  been  treated  in  various  ways,  and 
during  the  past  six  months  has  shown  signs  of  improvement,  under  a 
dressing  of  vaseline,  turpentine,  and  creosote.  The  backs  of  both  hands 
show  many  keratoses,  but  the  usual  telangiectases  are  remarkable  for  their 
absence.  On  the  back  of  both  wrists  is  an  area  about  the  size  of  a  pea, 
which  is  hard,  not  sore,  ulcerated  in  the  center,  with  indurated  edges, 
presenting  the  characteristic  appearance  of  an  epithelioma.  A  similar 
growth  started  three  months  ago  on  the  left  forehead.  This  soon 
acquired  raised  and  everted  edges  and  was  operated  upon  by  a  surgeon 
in  Hartford,  but  in  a  month  had  recurred,  and  was  larger  than  before. 
It  was  again  excised,  but  rapidly  returned.  On  examination  of  the  fore- 
head there  appeared  a  growth  about  the  size  of  a  quarter,  gangrenous  in 
the  center,  with  palisaded  edges.     There  was  induration  about  it,  and  the 


384  PORTER. 

growth  was  firmly  fixed  at  the  center  to  the  underlying  tissues.  No 
glands  could  be  made  out  in  the  parotid  region  or  at  the  angles  of  the  jaw. 

Operation  Jan.  17,  1908;  ether.  After  thorough  disinfection  with 
pure  carbolic  acid,  the  growth  on  the  forehead  was  excised  with  an  ample 
margin,  removing  a  circle  of  tissue  about  two  inches  in  diameter.  The 
incision  was  carried  down  to  the  periosteum,  which  was  removed  with  the 
growth.  Section  of  the  tumor  showed  that  it  involved  the  periosteum. 
On  this  account,  the  outer  table  was  chiselled  away  for  an  area  the  size  of 
a  half  dollar,  and  the  inner  table  was  also  removed,  over  an  area  the  size 
of  a  quarter,  exposing  the  dura  and  the  mucous  membrane  lining  the 
frontal  sinus.  A  complicated  plastic  operation  was  done,  and  the  wound 
closed  without  drainage.  The  two  epitheliomata  over  the  wrists  were 
excised  and  the  skin  sutured.  Next,  with  considerable  margin,  the 
ulcerated  and  thickened  skin  over  the  back  of  the  hand  was  removed  down 
to  the  veins,  subcutaneous  tissue,  and  tendons.  A  rather  thick  Thiersch 
graft  was  applied  and  sutured  in  position  with  firm  pressure.  The  graft 
grew  by  primary  union,  except  for  a  small  area  at  the  base  of  the  little 
finger,  which  healed  within  a  few  weeks.  Patient  discharged  at  the  end 
of  ten  days. 

The  two  discrete  epitheliomata  from  the  wrist  were  lost.  The  micro- 
scopical examination  from  the  skin  of  the  back  of  the  hand  by  Dr.  J.  H. 
Wright  was  as  follows :  The  surface  of  the  portion  of  skin  removed 
is  covered  with  crusts,  scabs,  and  discrete  and  confluent  wart-like  eleva- 
tions. After  fixation  in  Zenker's  fluid,  paraffine  sections  were  prepared 
from  six  different  places.  The  lesions  found  in  these  may  be  summarized 
as  follows  :  "  The  stratum  corneum  is  very  much  thicker  than  normal,  and 
shows  cyst-like  cavities  of  varying  size  containing  hyaline  material.  The 
stratum  germinativum  in  places  is  either  thicker  or  thinner  than  normal, 
and  the  interpapillary  processes  are  irregularly  variable  in  size  and  shape  or 
are  wanting.  In  a  few  places  the  cells  of  this  stratum  show  atrophy  with 
exaggeration  of  the  intercellular  spaces  and  there  is  infiltration  with  leu- 
cocytes. The  cells  of  this  stratum  also  show  some  imperfect  cornification. 
In  one  section  two  circular  masses  of  cornified  epithelium,  like  the 
"  pearls  "  of  epidermoid  carcinoma,  are  present  in  interpapillary  processes. 
In  another  section  over  a  small  area,  the  stratum  germinativum  is  pro- 
longed into  small  columns  of  atypical  epithelial  cells  which  lie  in  the 
superficial  portions  of  the  corium.  In  the  corium  about  the  cell  masses 
is  some  infiltration  by  cells  of  the  lymphoid  series.  I  am  inclined  to 
interpret  these  appearances  as  indicating  an  incipient  carcinoma  at  this 
point.  The  corium  generally  shows  an  increase  of  its  connective  tissue 
over  the  normal,  and  this  connective  tissue  in  places  is  in  the  condition  of 
hyaline  degeneration.  The  papillie  vary  considerably  in  size  and  in 
places  contain  greatly  dilated  capillaries.  Some  papillns  are  in  a  condition 
of  myxomatous  degeneration  and  some  others  show  more  or  less  transfor- 
mation of  the  connective  tissue  into  hyaline  material.  In  places,  small 
areas  of  the  corium  are  infiltrated  with  cells  of  the  lymphoid  series. 


SURGICAL   TREATMENT   OF   X-RAY   CARCINOMA.         385 

Examination  of  the  recurrent  tumor  on  the  forehead  brings  out  a  differ- 
ence of  opinion  between  Dr.  Wolbach  and  Dr.  Wright. 

(See  Plate  XXXVIII.,  Fig.  22.)  Pathological  report  by  Dr.  Wolbach. 
Tissue  from  forehead.  The  sections  consist  of  tumor  tissue  with  adjoin- 
ing necrotic  tissue.  No  normal  tissue  in  sections,  except  for  a  narrow 
strip  of  dense  fibrous  tissue  on  one  edge  of  a  few  sections.  The  micro- 
scopic picture  is  that  of  invading  cells  or  of  cells  having  proliferated  in  situ, 
distending  the  meshes  of  connective  tissue.  There  are  bands  of  dense 
collagen  fibrils  separated  by  large,  irregularly  shaped  cells,  many  in  stages 
of  mitosis.  That  the  connective  tissue  present  is  not  wholly  the  product  of 
the  tumor  is  shown  by  the  presence  of  normal  nerve  bundles.  Between 
the  tumor  cells  and  between  small  groups  of  cells  there  is  in  places  only 
a  small  amount  of  collagen  fibrils  (Mallory  connective  tissue  stain).  The 
tumor  cells  are  very  irregular  in  shape  and  in  size.  Many  are  multinu- 
cleated. There  is  no  definite  arrangement  of  cells  and  in  places  the  appear- 
ance suggests  that  these  cells  may  have  arisen  in  situ  by  multiplication  of 
preexisting  cells.  In  other  places,  the  picture  is  definitely  that  of  a 
tumor.  The  nuclei  are  large,  and  each  contains  a  large  nucleolus.  Where 
numerous  nuclei  exist  in  a  single  large  cell,  the  nucleoli  are  unusually  con- 
spicuous in  each  nucleus.  Mitoses  are  abundant  in  all  portions  of  the 
sections.  Multipolar  mitoses  are  common.  The  smaller  tumor  cells  are 
round,  oval,  and  spindle-shaped.  The  larger  very  irregular  in  outline 
and  usually  have  many  slender  processes.  A  few  tumor  cells  show  deli- 
cate fibrils  (Mallory  fibroglia  stain)  running  parallel  to  the  long  diameter. 
For  this  reason  and  because  of  the  arrangement  of  the  tumor  and  the 
apparent  presence  of  intercellular  collagen  fibrils  the  tumor  should  be 
classed  as  a  sarcoma  of  connective  tissue  origin. 

Pathological  report  by  Dr.  J.  H.  Wright:  "In  accordance  with  your 
request  I  confirm  my  verbal  report  to  you  made  some  time  ago  upon  my 
views  as  to  the  nature  of  the  tumor  of  the  forehead  in  the  case  of  Mr.  G . 
Although  the  histological  character  of  this  tumor  is  very  suggestive  of 
sarcoma,  I  believe  that  the  essential  cells  are  of  epidermal  origin,  and 
that  the  tumor  should  be  regarded  as  carcinoma  originating  from  the 
epithelium  of  the  skin  of  the  forehead.  I  am  led  to  this  belief  for  the 
following  reasons :  the  situation  of  the  tumor,  the  presence  of  fibrillation 
in  some  of  the  cells  reminiscent  of  the  fibrils  of  the  cells  of  the  epidermis, 
and  the  existence  at  the  periphery  of  some  of  the  cells  of  structures 
strongly  resembling  the  characteristic  'prickles'  of  the  epidermal  cells." 

Quotation  from  letter,  March  6,  1908:  "  My  hand  has  healed  in  good 
shape  and  most  of  the  thickened  spots  on  my  fingers  are  disappearing.  I 
can  about  half  shut  my  hand.  My  forehead  is  all  right  except  for  some 
tightness  of  the  skin  and  absence  of  normal  sensation.  The  spot,  where 
the  growth  had  been,  is  tight  and  does  not  move." 

Examination,  Aug.  5,  1908.  Sensation  has  been  gradually  coming 
back  to  forehead,  which  he  can  wrinkle  almost  normally.  There  is  very 
slight  thickening  on  the  inner  side  of  right  eyebrow  where  the  flap  was 
reflected.     The  scars  are  hardly  visible.     There  is  no  induration  or  pain 


386  PORTER. 

suggesting  any  recurrence  of  the  disease.  The  back  of  the  left  hand  is 
entirely  healed  ;  the  graft  is  movable  over  the  underlying  structures.  The 
backs  of  the  fingers  still  show  keratoses,  which  he  is  cutting  and  paring 
off.  He  can  flex  and  extend  fingers  normally.  In  every  respect  a  most 
excellent  result. 

Sinmnary  ;  Intermittent  ulceration  of  back  of  left  hand  for  seven  years, 
improving  for  the  past  six  months ;  excision  down  to  aponeuroses  and 
tendons ;  successful  skin  grafting.  Microscopic  examination  showed  com- 
mencing epithelioma.  The  longest  case  of  persistent  ulceration,  without 
cancer,  in  the  series.  Thrice  recurrent  growth  of  forehead,  which  involved 
the  periosteum :  removal  of  bone  down  to  dura  and  frontal  sinus :  com- 
plicated plastic  operation.  Opinions  differ  as  to  the  nature  of  the  growth  ; 
Dr.  Wolbach  classifying  it  as  a  sarcoma ;  Dr.  Wright  believes  it  to  be  a 
carcinoma.     One  year  after  operation,  no  evidence  of  recurrence. 

Case  XVIII.  — Personal.  (Plate  XXXVII.,  Figs.  13,  14,  and  15.)  J. 
G. ;  34  years  ;  X-ray  operator.  Patient  has  suffered  for  several  years  from 
the  milder  forms  of  X-ray  lesions,  atrophy  of  the  sweat  glands,  eczema,  rib- 
bing of  the  finger  nails,  telangiectases  and  keratoses.  During  the  winter 
he  has  a  great  deal  of  pain  and  trouble  from  fissures  over  the  extensor 
surfaces  of  the  joints.  In  May,  1906,  numerous  excoriations  and  fissures 
were  excised  and  successfully  grafted.  On  Sept.  15,  1906,  there  was  a 
recurrence  of  ulceration  near  the  radial  border  of  the  terminal  phalanx  of 
the  ring  finger.  On  October  18  this  ulceration  was  freely  excised,  and 
the  radial  fourth  of  the  nail  with  its  matrix  extirpated.  The  skin  at  the 
margin  of  the  nail  was  approximated  with  plaster  and  another  graft 
applied:  sound  healing  in  ten  days. 

Pathological  report  by  Prof.  F.  B.  Mallory  of  the  Harvard  Medical 
School:  "The  section  shows  a  small  mass  of  actively  proliferating  con- 
nective tissue  cells,  covered  with  epidermis,  which  is  edematous  and 
contains  fairly  numerous  mitotic  figures.  At  one  or  two  points  the 
epidermis  is  lacking,  and  a  little  granulation  tissue  has  formed.  In  these 
areas,  and  beneath  the  epidermis,  is  a  small  amount  of  infiltration  with 
cells  (chiefly  lymphocytes)  of  inflammatory  origin.  The  proliferating 
connective  tissue  cells  occur  diffusely  scattered  among  the  bundles  of 
collagen  fibrils  of  the  corium.  Mitotic  cells  are  numerous  and  often 
multiple.  Many  of  the  resulting  cells  are  large  and  often  contain  large 
lobulated  or  multiple  nuclei.  The  lesion  is  an  active,  in  some  ways 
atypical,  proliferation  of  connective  tissue  cells.'' 

The  finger  remained  healed  until  the  middle  of  March,  1907,  when  the 
distal  part  of  the  graft  on  the  radial  side  began  to  increase  in  size  and 
show  well  marked  vascularity.  After  two  weeks  there  was  a  slight  dis- 
charge near  the  edge  of  the  nail.  By  April  23,  1907,  the  growth  had 
become  decidedly  larger  and  was  apparently  extending  backward  into  the 
proximal  graft.  The  terminal  joint  was  accordingly  amputated  under  gas 
and  ether  ;  primary  union. 
Pathological  report  by  Prof.  F.  B.    Mallory  of  the   Harvard    Medical 


SURGICAL   TREATMENT    OF    X-RAY    CARCINOMA.         387 

School  (see  Plate  XXXVII.,  Fig.  15)  :  "  The  section  shows  an  oval,  cell- 
ular mass  of  tissue,  partially  surrounded  by  more  or  less  normal  fibrous 
tissue.  The  cellular  mass  at  its  outer  end  is  ulcerated  and  covered  with 
fibrin,  cells,  and  dried  necrotic  tissue.  The  more  normal  tissue  is  covered 
with  epidermis.  The  oval  cellular  mass  of  tissue  is  quite  sharply  defined 
and  is  limited  by  a  layer  of  dense,  fibrous  tissue.  It  is  composed  of 
rapidly-growing  connective  tissue  cells  and  of  a  small  number  of  thin- 
walled  blood  vessels.  The  connective  tissue  cells  are  typical,  that  is,  they 
have  flat,  oval  nuclei,  and  contain  one  to  three  coarse  chromatin  masses. 
The  cytoplasm  is  made  out  with  difficulty.  In  places  the  cells  are 
bordered  by  very  delicate  fibroglia  fibrils.  Everywhere  the  cells  are  sepa- 
rated from  each  other  by  a  relatively  large  amount  of  ordinary  (collage- 
nous) fibrils.  The  cells  and  their  fibrils  tend  to  form  small  bundles  which 
run  in  all  directions.  Mitotic  figures  are  numerous,  one  to  three  showing 
in  nearly  every  oil  immersion  field.  While  the  cellular  mass  of  tissue  at 
its  base  is  sharply  defined,  on  both  sides,  it  gradually  blends  with  the 
adjoining  connective  tissue.  The  adjoining  tissue  of  the  finger  shows 
infiltration  with  numerous  groups  of  lymphocytes.  Otherwise  there 
appears  to  be  no  change  in  it.  It  is  difficult  to  give  a  positive  diagnosis 
in  this  case.  The  rapidly-growing  mass  of  connective  tissue  may  be  either 
an  unusual  form  of  reparative  action  on  the  part  of  connective  tissue  or  it 
may  be  a  connective  tissue  new  growth,  namely,  a  rather  slow-growing 
spindle  cell  sarcoma.  Personally  I  favor  the  former  view,  owing  to  the 
lack  of  any  definite  evidence  as  yet  of  invasion." 

The  finger  remained  well  until  August,  1908,  when  on  the  ulnar  side  of 
the  same  there  appeared  an  induration  in  the  skin  which  was  neither 
tender  nor  painful,  but  gradually  grew  until  it  was  the  size  of  an  old- 
fashioned  three-cent  piece.  There  was  no  ulceration,  the  tumor  had  slight 
vascularity  and  was  movable  to  some  extent  upon  the  underlying  struct- 
ures. In  view  of  the  doubt  as  to  the  true  pathology  of  the  recurrent 
growths  on  this  finger,  amputation  at  the  interphalangeal  joint  was  per- 
formed in  November,  1908  ;  primary  union. 

Pathological  report  by  Prof.  F.  B.  Mallory  of  Harvard  Medical  School : 
"  This  lesion,  like  No.  2,  is  quite  definitely  outlined.  In  places  at  the 
periphery,  however,  the  cells  extend  among  the  bundles  of  old  collagen 
fibrils  of  the  corium.  The  tissue  is  fairly  cellular  and  contains  mitotic 
figures,  but  they  are  not  so  numerous  as  in  lesions  i  and  2,  and  are  rarely 
atypical.  The  cells  and  fibrils  are  separated  by  a  small  amount  of  fluid 
(edema).  The  sections  from  these  lesions  show  masses  of  rapidly-prolif- 
erating connective  tissue  cells.  In  numbers  i  and  2,  especially,  the  cells 
are  often  atypical.  The  mitoses  are  frequently  multiple  and  large  multi- 
nucleated cells  result  from  them.  All  these  lesions  suggest  the  possibility 
of  being  fibrosarcomata.  It  seems  wisest  for  the  present,  however,  to 
regard  them  as  more  or  less  atypical  growths  of  connective  tissue  cells 
under  conditions  not  fully  understood.  If  later  it  should  be  proved  that 
X-rays  cause  similar  connective  tissue  growths  which  give  rise  to  metas- 
tases or  to  evident  invasion  of  other  tissues  (true  fibrosarcomata),  these 


388  PORTER. 

lesions  might  be  regarded  as  of  a  similar  nature,  but  at  present  such  an 
assumption  is  not  justifiable." 

Pathological  report  by  Dr.  Wolbach.  Amputation  of  middle  pha- 
langeal joint  of  ring  finger,  left  hand.  Beneath  the  skin  of  the  distal 
portion  on  the  ulnar  side  of  dorsal  surface  is  a  firm,  resilient,  yellowish, 
ovoid  nodule,  .8  x  .6  centimeter  in  diameter.  This  nodule  is  completely 
covered  by  epidermis  and  is  not  attached  to  the  bone  or  tendon. 

Microscopic  examination  :  The  nodule  is  composed  of  loose  cellular  con- 
nective tissue,  the  cells  of  which  form  bundles  and  whorls  running  in  all 
directions.  The  amount  of  collagenous  intercellular  substance  is  much 
greater  than  that  in  the  first  specimen  removed  and  examined  by  Dr. 
Mallory.  The  collagenous  fibrils  are  more  widely  separated  than  in 
normal  connective  tissue,  suggesting  a  slight  amount  of  edema.  The 
cells  resemble  those  of  normal  connective  tissue.  The  nodule  is  fairly 
sharply  demarcated  from  the  immediately  surrounding  practically  normal 
connective  tissue  of  the  corium  by  means  of  the  concentric  flattened 
arrangement  of  the  cells  and  fibrils  of  the  latter.  There  is  no  definite 
capsule.  There  is  no  evidence  of  invasion.  There  are  numerous  mitotic 
figures  throughout  the  nodule,  all  of  them  normal  in  type.  The  tissue  is 
supplied  with  numerous  small,  thin-walled  vessels  and  capillaries,  uni- 
formly distributed.  The  epidermis  covering  the  nodule  consists  of  a 
smooth  thin  layer  lying  directly  upon  the  tissue  described  and  which  pre- 
sents an  unbroken  convex  surface.  The  horny  layer  of  this  covering  epi- 
dermis is  thin.  The  stratum  germinativum  is  poorly  differentiated  ;  it 
consists  mainly  of  slightly  swollen  pale-staining  prinkle  cells  of  fairly 
uniform  size.  The  deepest  layer  is  regularly  apposed  to  the  underlying 
tissue  in  the  manner  of  normal  epidermis.  Where  the  nodule  adjoins  the 
normal  tissue  there  is  a  deep  downgrowth  of  epidermis  in  the  form  of 
slender  stalks  partially  embracing  the  new  tissue.  The  surrounding  epi- 
dermis is  slightly  hypertrophic  and  shows  slight  irrelevant  changes.  A 
positive  diagnosis  is  not  possible  in  this  case,  as  the  same  discussion  used 
by  Dr.  Mallory  in  his  description  of  the  tissue  removed  applies  here. 
Against  the  view  that  the  tissue  is  granulation  tissue  is  the  lack  of  signs  of 
active  inflammation,  the  presence  of  unbroken  epidermis  and  the  absence 
of  a  vascular  arrangement.  Favoring  the  view  that  we  are  dealing  with  a 
slowly-growing  connective  tissue  tumor  (fibrosarcoma)  is  the  presence  of 
numerous  mitoses,  and  against  this  view  is  the  lack  of  evidence  of  invasion. 

Suminary :  Mild  chronic  X-ray  lesions,  numerous  skin  grafts  for  kera- 
toses and  fissures  over  knuckles.  Primary  union.  Recurrent  growth  of 
the  matrix  of  ring  finger  nail,  left  hand  ;  amputation.  Occurrence  of  a 
fibrous  tumor  on  the  ulnar  side  of  stump  one  year  afterwards  ;  amputation 
through  first  phalanx.  Pathologists  differ  as  to  the  character  of  this 
growth,  some  believing  it  to  be  an  unusual  form  of  granulation  tissue ; 
others  classifying  it  as  a  sarcoma. 

Case  XIX.  —  Personal.  (Plate  XXXVII.,  Figs.  i6,  17,  18.)  W.  J.  D. 
(physician)  ;  32  years.     X-ray  operator.     Began  work  with  a  large  static 


SURGICAL   TREATMENT   OF   X-RAY    CARCINOMA.         389 

machine  in  March,  1896;  in  October  of  same  year  a  powerful  twelve-inch 
coil  was  used.  In  November,  1896,  the  first  severe  dermatitis  took  place. 
This  subsided  under  treatment,  but  was  followed  in  April,  1897,  by  an 
extremely  severe  general  dermatitis  with  pain  beyond  description.  All 
kinds  of  washes,  ointments,  and  powders  were  used  with  orthoform  to 
relieve  the  pain.  My  first  graft  was  applied  to  an  ulcer  on  the  tip  of  the 
left  forefinger  on  July  10,  1897.  On  Aug.  13,  1897,  fourteen  different 
grafts  were  applied  after  excision  of  as  many  ulcerated  areas.  The 
extreme  pain  ceased  at  once  and  the  great  majority  of  the  grafts  healed 
soundly.  Between  this  date  and  1902  there  were  seven  other  similar 
operations  under  ether.  Most  of  the  grafts  were  successful,  but  in  spite 
of  several  attempts  failure  was  constant  over  ulcerations  on  the  ends  of 
the  ring  finger  of  both  hands. 

In  July,  1902,  another  attempt  at  excision  and  grafting  was  made;  it 
failed.  In  October,  extremely  painful,  angry  looking  ulcers  with  indurated 
edges  had  formed  upon  the  ends  of  both  ring  fingers,  these  were 
amputated.  The  report  from  the  pathologist  was  unmistakable  carci- 
noma. In  consequence,  on  Oct.  31,  1902,  both  of  the  ring  fingers 
were  amputated  at  the  knuckles.  From  October,  1902,  until  June,  1905, 
a  dozen  or  more  operations  consisting  of  partial  amputations,  excision 
of  growing  ulcerations  and  keratoses  were  performed.  In  May,  1905, 
for  the  first  time  in  eight  years,  the  patient  was  free  from  pain  and 
no  dressings  had  to  be  worn.  In  June,  the  left  hand  was  practically  well, 
but  keratoses  broke  down  on  the  base  of  the  middle  finger  of  the  right 
hand,  and  there  was  some  ulceration  near  the  matrix  of  the  thumb  nail. 
In  November,  1905,  an  undoubted  epithelioma  was  excised  from  the  base 
of  the  third  finger  of  the  right  hand,  and  numerous  other  ulcerations  were 
skin  grafted  ;  some  of  these  showed  a  precancerous  stage. 

By  April,  25,  1907,  after  ten  years  of  treatment,  and  twenty-five  opera- 
tions under  ether,  the  condition  of  the  hands  was  as  follows  :  Left  hand  : 
amputation  of  little  finger  through  the  interphalangeal  joint ;  amputation  of 
ring  and  middle  fingers  at  knuckles  ;  fourth  finger  shows  slight  ulceration  at 
its  base,  and  a  small  ulcer  in  the  middle  of  the  back  of  the  hand ;  there  are 
numerous  keratoses,  but  no  ulcerations.  Right  hand :  the  thumb  is  use- 
ful, but  its  ulnar  side  is  covered  with  thickened  epithelium  at  the  base  of 
which  is  a  small  ulceration.  For  two  months  there  has  been  ulceration 
over  the  joint  between  the  first  and  second  phalanx  of  the  forefinger,  with 
flexion  of  this  joint ;  this  ulceration  strongly  suggests  malignant  disease. 
The  middle  finger  is  stiff,  the  fourth  is  lacking,  as  is  also  the  end  of  the 
fifth.  The  hand  shows  the  presence  of  numerous  grafts  which  have  taken, 
and  a  few  keratoses.  The  patient  was  at  work  at  a  medical  school,  and 
did  not  submit  to  an  operation  until  July  5,  1907,  at  which  time  it  was 
evident  that  the  forefinger  must  be  amputated,  for  undoubted  epithelioma- 
tous  ulcerations  were  forming  in  several  parts  of  the  dorsum  of  the  finger, 
notably  about  the  opening  into  the  joint  before  mentioned.  Under  ether, 
the  forefinger  was  amputated  at  the  middle  of  the  first  phalanx,  a  palmar 
flap  of  sound  skin  being  reflected  backward.     Several  suspicious   areas 


390  PORTER. 

were  exxised  in  other  parts  of  both  hands,  and  skin  grafted.  Microscopic 
examination  of  the  amputated  forefinger  showed  five  diiTerent  areas  of 
carcinoma,  which  owing  to  delayed  operation  had  infiltrated  deeply  the 
subcutaneous  tissues,  surrounded  the  digital  nerves  on  the  radial  side,  and 
caused  the  extreme  pain  (see  Plate  XXX VII.,  Fig.  i6).  The  columns  of 
epithelial  cells  had  penetrated  to  the  periosteum.  As  aresult  of  this  examina- 
tion it  was  decided  on  July  15  to  amputate  higher  up.  The  head  of  the  first 
metacarpal  bone  was  removed  and  a  large  flap  reflected  onto  tiie  dorsum  of 
the  hand,  thus  forming  a  sound  stump  for  approximation  of  the  thumb. 

In  September,  1908,  after  eating  lobsters,  there  occurred  a  general 
urticaria  and  both  hands  became  much  swollen  and  the  serous  discharge 
was  extreme.  The  patient  was  confined  to  bed  for  ten  days,  then 
very  gradually  the  exudate  dried  up  and  there  followed  desquamation. 
This,  however,  did  not  affect  the  keratotic  areas.  There  have  been  one 
or  two  injuries  to  the  base  of  the  forefinger  of  the  left  hand,  and  to  the 
base  of  the  middle  finger  of  the  right  hand,  which  set  up  extremely  pain- 
ful and  obstinate  excoriations.  For  several  months  there  has  been  an 
inflamed  warty  growth  over  the  stump  of  the  little  finger  of  the  left  hand. 

Examination  and  operation  Dec.  7,  1908  (see  Plate  XXXVII  ,  Fig.  18). 
Over  the  head  of  the  ulna,  on  the  left,  are  two  irritated  thickened  exco- 
riated areas,  which  are  being  continually  injured  by  the  cuff  Over  the 
center  of  the  hand  there  is  a  small,  tender,  deep  ulceration  about  the 
size  of  a  split  pea.  Over  the  base  of  the  forefinger,  and  along  the  ulnar 
side  of  the  thumb  are  keratoses  cracks  and  fissures.  The  left  hand  was 
the  first  operated  upon.  The  warty  growth  on  the  little  finger  was 
excised  down  to  the  aponeurosis  and  submitted  to  Dr.  Whitney,  who 
reported  epithelioma.  The  question  arose  as  to  whether  the  finger 
should  be  amputated  at  the  knuckle  or  whether  more  conservative  meas- 
ures were  justifiable,  owing  to  the  usefulness  of  this  finger.  I  decided  to 
remove  a  slightly  larger  margin  down  to  the  aponeurosis,  which  was  then 
thoroughly  cauterized  with  the  Paquelin  cautery.  The  other  areas 
described  were  deeply  shaved,  and  skin  grafted  just  back  of  the  first 
interphalangeal  joint,  and  another  about  the  center  of  the  middle  phalanx 
were  also  excised  and  grafted.  After  this  operation  the  remainder  of  the 
left  hand  seemed  in  good  condition.  There  was,  of  course,  atrophy  of 
the  hair,  some  telangiectases,  large  areas  covered  by  grafts  and  cicatricial 
tissue.  The  condition  of  the  right  hand  was  as  follows :  the  middle 
finger  is  partially  flexed  and  there  is  hyperextension  at  the  first  interpha- 
langeal joint.  There  is,  however,  flexion  at  the  knuckle.  The  worst 
lesion  seems  to  be  excessive  hypertrophy  and  keratosis  of  the  skin,  over 
knuckle  of  little  finger,  as  shown  in  the  photographs.  This  spot  is  fie- 
quently  subjected  to  slight  trauma.  There  are  similar  inflamed  and  tliick- 
ened  areas  on  the  radial  side  of  the  first  knuckle,  and  along  the  ulnar 
side  of  the  thumb.  The  nail  of  the  thumb  is  deformed  and  split  on  the 
ulnar  side  of  the  median  line,  where  granulation  tissue  and  hypertrophied 
matrix  keep  up  a  chronic  sore.  There  exists  over  the  ulnar  bone, 
similar  to  the  left  hand,  an  area  of  thickened  epithelium  which  is  irritated 


SURGICAL   TREATMENT   OF   X-RAY    CARCINOMA.         39 1 

by  the  cuff.  At  the  base  of  the  middle  finger  there  are  several  keratoses. 
The  ulnar  half  of  the  thumb  nail  was  removed,  and  with  curette  and  knife 
the  matrix  was  thoroughly  eradicated.  The  area  over  the  base  of  the 
middle  finger  was  excised  down  to  the  cicatricial  tissue,  exposing  a  small 
part  of  the  tendon  in  the  median  line.  All  of  the  keratoses  were  shaved 
off  with  a  knife  and  grafted.  It  was  quite  remarkable  at  this  operation 
to  see  the  hemostatic  action  of  the  grafts.  Once  placed  in  position, 
bleeding  quickly  diminished,  and  in  a  few  moments  practically  ceased. 
Both  hands  were  placed  upon  splints,  the  forearm  held  in  position  by 
adhesive  plaster,  and  the  grafts  covered  with  small  strips  of  protective 
tissue.  Two  keratoses  were  excised,  one  from  the  forehead  and  the 
other  from  the  inner  part  of  the  upper  eyelid. 

Dec.  20,  1908.  The  large  and  important  graft  over  the  knuckle  of 
the  middle  finger  has  healed  soundly,  as  have  five  other  grafted  areas  on 
the  right  hand  ;  grafts  upon  two  small  keratotic  areas  failed.  The  grafts 
placed  on  the  left  hand,  however,  have  not  been  so  successful,  owing  to 
hemorrhages  underneath  them.  Only  two  out  of  five  have  taken.  The 
base  of  the  little  finger,  which  was  cauterized,  has  been  extremely  painful, 
and  is  granulating  very  slowly. 

A  more  careful  pathological  report  showed  epithelioma  at  the  site  of 
the  excision  on  the  little  finger  of  the  left  hand,  and  commencing  epithe- 
lioma over  the  knuckle  of  the  right  middle  finger.  All  of  the  other  areas 
excised  were  negative. 

Jan.  20,  1909.  In  spite  of  various  sorts  of  dressing  the  ulceration 
after  cauterization  of  the  little  finger  has  been  persistently  and  exquisitely 
sensitive  and  painful,  causing  loss  of  sleep  and  necessitating  opiates 
and,  locally,  Schleich's  solution.  To-day  egg  membrane  was  tried,  and 
gave  such  marked  relief  that  several  skin  grafts  were  applied  as  a  dress- 
ing, though  from  the  character  of  the  granulations  it  seemed  unlikely 
that  they  would  grow.  The  pain  was  immediately  relieved,  and  much  to 
our  surprise  part  of  the  grafts  "took"  and  slowly  extended  downward 
over  the  ulcer.  Progress  ceased,  however,  by  February  10,  and  in  view 
of  the  extreme  pain  and  danger  of  recurrence  it  seemed  as  if  the  attempt 
to  save  the  finger  had  been  a  mistake.  It  was  decided,  therefore,  that  if 
the  next  attempt  at  grafting  proved  unsuccessful  that  amputation 
should  be  done.  On  Feb  19,  1909,  under  ether,  the  ulceration  was 
thoroughly  disinfected  and  carefully  shaved  down  to  a  smooth  base. 
Thin  grafts  were  used  and  held  in  position  by  protective  strips.  Several 
other  areas  were  excised  and  similarly  treated,  the  majority  of  which 
grew,  but  at  the  end  of  two  days  infection  occurred  in  the  little  finger, 
and  all  of  the  grafts  came  away.  Pain,  however,  has  been  distinctly  less 
after  the  last  operation  and,  in  a  few  days,  epidermis  began  to  grow  from 
the  former  grafts  and  the  edges  of  the  wound,  so  that  by  March  i,  1909, 
spontaneous  healing  was  complete. 

Suinmary :  Commencing  with  July  10,  1S97,  I  have  operated  upon  this 
patient  under  ether  thirty-two  times,  the  operations  varying  in  duration 
from  one  hour  and  a  half  to  three  hours.     At  present  there  remains  of  his 


392  PORTER. 

left  hand  two  joints  of  the  little  finger,  the  forefinger  and  thumb  ;  of  the 
right  hand,  the  thumb,  the  middle  finger,  barring  part  of  the  terminal 
phalanx,  and  one  and  a  half  phalanges  of  the  little  finger.  More  than  half 
of  the  skin  of  the  backs  of  both  hands  consists  of  Thiersch  grafts.  From 
the  initial  dermatitis  there  has  been  continual,  though  slight  enlargement 
of  the  axillary  glands,  but  no  evidence  of  recent  increase  in  size,  or  any 
suggestion  of  metastases.  There  was  undue  and  dangerous  delay  in  am- 
putating the  cancerous  forefinger  of  the  right  hand.  With  this  exception, 
epitheliomatous  ulcerations  have  been  excised  early.  For  two  months  it 
seemed  as  if  the  attempt  to  save  the  stump  of  the  little  finger  was  a  failure, 
but  in  spite  of  the  severe  pain  the  patient  seemed  unwilling  to  sacrifice  it, 
owing  to  the  damaged  forefinger  and  the  fear  that  with  its  possible  loss  in 
the  future  the  thumb  would  have  nothing  to  press  against  in  grasping 
small  objects. 

The  number  of  different  carcinomata  in  this  one  case  has  been  over  a 
score.  I  have  no  doubt  that  general  metastases  would  have  taken  place 
long  ago  had  it  not  been  for  timely  excisions  and  amputations. 

Case  XX.  —  Personal.  F.J.  B.  (physician)  ;  34  years,  Baltimore,  Md. 
Began  X-ray  work  in  1900  and  suffered  at  the  start  from  an  acute  derma- 
titis. When  this  subsided,  all  finger  nails,  with  the  exception  of  those  on 
the  thumbs,  came  off.  After  six  months'  rest  the  dermatitis  cleared  up, 
and  all  of  the  nails  grew  again,  except  that  on  the  right  forefinger ;  this 
never  reformed.  In  the  spring  of  1902,  after  resumption  of  work  with  the 
X-ray,  there  was  no  active  dermatitis,  but  keratotic patches  formed  on  the 
hands  with  the  appearance  of  the  usual  telangiectatic  areas.  Gradually 
the  nails  became  deformed.  Up  to  this  time  there  was  little  pain  but 
considerable  stiffness  in  the  hands.  The  keratoses  increased  up  to  1905, 
when  the  first  ulcer  appeared  on  the  dorsum  of  the  left  hand  and  one  on 
the  right  forefinger  at  the  junction  of  the  second  and  third  phalanges. 
These  ulcerations  were  excised  and  numerous  keratoses  were  removed. 
The  ulcer  on  the  right  forefinger  returned  in  a  few  months  and  remained 
about  the  size  of  a  pea.  Numerous  attempts  were  made  to  heal  it  as  it 
was  exceedingly  painful,  but  these  were  not  successful.  The  keratosis  on 
the  base  of  the  right  finger  returned  after  excision  and  has  persisted  up  to 
the  present  time,  without  ulceration.  In  1906,  ulceration  began  in  a  small 
keratosis  which  had  been  present  for  several  years,  situated  on  the  external 
side  of  the  nail  of  the  ring  finger  of  the  right  hand.  This  has  since 
gradually  increased  in  size,  extending  along  the  outer  edge  of  the  nail,  and 
then  upwards  upon  the  dorsum  of  the  finger  almost  to  the  first  inter- 
phalangeal  joint.  The  pain  in  this  ulcer  for  the  last  nine  months  has  been 
very  intense,  so  that  for  many  nights  no  rest  could  be  obtained.  In  the 
fall  of  1907  the  matrix  of  the  right  forefinger  nail  broke  down  and  assumed 
the  character  of  a  sluggish  ulcer,  exquisitely  tender  and  painful.  The 
whole  matrix  was  destroyed.  At  present  the  dorsum  of  the  forefinger, 
almost  to  the  joint  between  the  first  and  second  phalanges  is  occupied  by 
a  raw,  beef  red  ulceration  without  induration.     This  resembles  in  a  striking 


SURGICAL   TREATMENT    OF   X-RAY    CARCINOMA.  393 

degree  the  ulcerations  which  occurred  on  the  ring  fingers  of  Case  XIX. 
"  The  pain  is  most  intense  and  is  best  described  as  a  sharp  shooting  neu- 
ralgic pain  of  the  worst  character.  It  lasts  two  or  three  seconds  and 
occurs  from  eight  to  ten  times  every  minute.  When  the  pain  was  of  this 
character  the  ulcer  always  appeared  raw  and  the  granulations  very  red. 
Next  would  come  the  formation  of  a  slough,  when  the  more  intense  pain 
would  disappear." 

Patient  entered  the  Massachusetts  General  Hospital  on  Jan.  19,  1909. 
Both  hands  presented  typical  X-ray  dermatoses  extending  up  to  the  wrists. 
There  were  numerous  keratoses  and  a  few  crusted  spots  The  chief  lesions 
have  already  been  described  —  the  raw  ulcerations  on  the  distal  phalanx 
of  the  first  and  ring  fingers  of  the  right  hand.  The  nail  of  the  middle 
finger  is  deformed  and  there  is  considerable  suppuration  about  the  thin 
and  cracked  edges  of  this  nail. 

Operation  Jan.  20,  1909,  under  ether.  As  I  feared  malignant  disease 
of  the  forefinger  and  the  ring  finger,  a  small  portion  from  the  forefinger 
ulceration  was  first  removed  and  given  to  Dr.  Whitney  for  rapid  exami- 
nation. Though  nothing  malignant  was  found,  I  determined  upon  amputa- 
tion of  the  ends  of  both  of  these  fingers,  owing  in  part  to  questionable 
malignancy,  but  chiefly  because  I  believed  that  the  grafts,  even  if  success- 
ful, would  ultimately  break  down.  Accordingly  a  transverse  incision  was 
made  down  to  the  bone,  through  the  skin,  just  below  the  first  interphalan- 
geal  joint.  The  skin  was  carefully  dissected  downward,  and  the  bone 
divided  at  the  middle  of  the  second  phalanx  ;  a  long  palmar  flap  of  healthy 
tissue  being  turned  backward  and  sutured  in  position.  This  gave  a  rough 
resemblance  to  the  crescent  of  the  finger  nail.  Numerous  keratoses  and 
minor  ulcerations  were  deeply  shaved  from  various  parts  of  both  hands 
and  skin  grafted.  All  wounds  were  dressed  with  protective,  and  carefully 
applied  pressure  held  the  grafts  in  firm  apposition.  There  occurred  at  the 
site  of  both  amputations  a  slight  degree  of  infection  which  delayed  healing. 
By  making  two  parallel  incisions  at  the  angle  of  the  nail  an  attempt  was 
made  to  extirpate  the  matrix  of  the  middle  finger  nail ;  the  pulp  of  the 
finger  was  grafted  ;  of  twenty  other  grafts,  eighteen  took.  The  patient 
was  discharged  on  February  14,  with  sound  union  in  the  amputations 
and  all  grafted  areas  looked  well. 

On  April  i,  patient  stated  that  he  had  been  entirely  free  from  pain 
since  leaving  the  hospital,  for  the  first  time  in  years.  About  the  matrix 
of  the  middle  finger  there  is  slight  suppuration,  and  from  the  sides  there 
has  been  some  reformation  of  soft  nail.  The  grafts  are  looking  very  well. 
After  consultation  it  was  decided  that  this  patient  should  be  allowed  to 
continue  the  use  of  the  X-rays  provided  he  never  exposed  himself  unpro- 
tected. 

Pathological  examination  by  Dr.  Whitney.  More  careful  examination 
of  the  tissues  removed  from  this  case  showed  that  in  both  forefinger  and 
ring  finger  there  was  undoubted  superficial  carcinoma ;  the  other  areas 
excised  were  negative. 


394  PORTER. 

Case  XXI.  —  Personal  communication  from  Dr.  L.  L.  McArthur,  of 
Chicago,  111.  S.  C.  G.  (physician),  who  combined  electrical  therapeutics 
from  a  static  machine  with  X-ray  pictures  ;  he  developed  his  own  plates. 
Chronic  dermatitis ;  ulceration  of  the  terminal  phalanges  of  first  and 
middle  finger  of  left  hand;  amputation  of  terminal  phalanges.  Later, 
there  developed  a  typical  epithelioma  on  the  remains  of  the  left  index  fin- 
ger, and  numerous  keratoses.  The  finger  was  amputated  and  found  to  be 
carcinomatous.  Keratoses  excised  and  grafted;  axilla  thoroughly  dis- 
sected.    No  glands  found  to  be  involved.     Patient  well  one  year  after. 

Summary  :  Epithelioma  of  left  index  finger ;  amputation  ;  dissection 
of  axilla.  No  glands  involved.  At  present  no  evidence  of  recurrence 
Prognosis  good. 

Case  XXII.  —  Personal  communication  from  Dr.  L.  L.  McArthur,  of 
Chicago,  111.  W.,  of  Chicago;  probably  the  first  X-ray  burn  on  record. 
Eleven  hours'  exposure  within  a  period  of  three  days.  Huge  burn  extend- 
ing from  the  symphysis  to  the  chin,  the  healing  of  which  required  several 
plastic  operations.  In  July,  1908,  having  been  well  in  the  interim,  he  was 
thrown  from  his  pony  and  injured  the  cicatrix.  The  ulcer  refused  to  heal 
and  carcinoma  rapidly  developed,  until  an  area  10  x  4  inches  had  become 
involved.  At  operation,  with  a  wide  margin,  the  cancerous  skin  was 
removed,  as  well  as  the  anterior  sheath  of  the  rectus,  part  of  the  rectus 
muscle,  and  in  parts  even  its  posterior  sheath.  By  undermining  the  skin 
laterally,  beyond  the  axillary  line,  the  wound  was  closed  anteriorly,  and 
though  infection  occurred,  healing  is  now  nearly  completed,  Dec.  11,  1908. 

Su)n7>iary  :  Severe  X-ray  burn  in  1896,  involving  the  chest  and  abdo- 
men ;  plastic  operations.  Latent  period  "eleven  years;"  extensive  car- 
cinoma of  abdominal  wall ;    radical  excision. 

Case  XXIII.  —  Personal  communication  from  Dr.  Charles  H.  Bowen,  of 
Columbus,  O.  L.  M.  E  (physician)  ;  has  been  doing  X-ray  work  for  the 
last  ten  years.  Nine  years  ago  he  developed  a  dermatitis  which  gradu- 
ally increased  in  severity  until  ulcers  developed.  These  ulcers  were 
curetted  from  time  to  time,  and  skin  grafts  were  tried,  but  seemed  of  no 
permanent  benefit.  The  grafts  would  take,  but  in  a  few  months  would 
break  down,  and  the  ulcerations  would  be  as  painful  as  ever.  His  phalan- 
ges were  amputated  on  a  number  of  occasions,  until  he  finally  lost  three 
fingers  from  his  left  hand  and  two  from  the  right.  Several  months  ago 
he  developed  an  ugly  ulcer  on  the  back  of  his  left  hand,  which  gradually 
became  an  epithelioma.  This  was  curetted  on  several  occasions,  but 
without  effect.  The  remains  of  the  right  hand  is  so  painful  that  it  has  to 
be  kept  continually  covered  in  a  layer  of  cotton  in  order  to  avoid  the 
slightest  injury.  In  April,  1908,  the  left  forearm  was  amputated  at  the 
middle.  In  December,  1908,  no  evidence  of  recurrence  on  the  left. 
The  right  hand,  which  had  quite  a  number  of  very  suspicious  looking 
ulcers,  has  been  gradually  getting  better,  under  large  amounts  of  iodine, 


SURGICAL   TREATMENT    OF   X-RAY    CARCINOMA.         395 

though  not  necessarily  caused  by  it.     X-ray  work  and  medicine  have  been 
given  up.     There  is  no  evidence  of  metastases. 

Siimmary  :  X-ray  worker  ;  persistent  ulcerations  and  deep  epithelioma 
necessitating  amputation  of  left  forearm  at  the  middle.  Persistent 
ulcerations  of  right  hand  required  amputation  of  two  fingers.  Recently, 
ulcerations  on  the  back  of  the  hand  have  improved,  while  taking  iodine 
and  giving  up  work. 

Case  XXIV.  —  M.  W. ;  X-ray  manufacturer  ;  static  machines  ;  has  suf- 
fered for  years  with  the  severer  grades  of  dermatitis ;  recently  multiple 
epitheliomata  have  developed  on  the  hands  and  fingers.  After  several 
operations  there  remains  on  the  right  hand  the  thumb  and  forefinger ; 
on  the  left  hand  the  thumb,  index,  and  middle  fingers  —  the  fourth  and 
little  fingers,  with  their  metacarpal  bones,  have  been  removed.  There  are 
other  lesions  on  the  face  and  back. 

Case  XXV.  —  F.  D.  A.  (physician);  radiologist,  Rochester,  N.Y. 
Amputation  of  left  hand ;  X-ray  carcinoma  ;  Journal  American  Medical  As- 
sociation, Dec.  12,  1908.  Personal  communication  from  Dr.  J.  Kevins 
Hyde  and  Dr.  Ormsby  of  Chicago  ;  two  private  patients  never  reported. 

Case  XXVI.  —  O.  R.  ;  severe  X-ray  lesions  after  treatment  for  plantar 
keratodermia  :  epithelioma  ;  excisions  of  soles  of  both  feet ;  Krause  graft- 
ing successful. 

Case  XXVII.  —  P.  J.  S.  ;  epithelioma  of  back  of  hand,  following 
X-ray  lesions. 

Cases  XXVIIL,  XXIX.,  XXX.,  XXXI. —Four  cases  of  carcinoma, 
operated  upon  by  Dr.  Sick  of  Hamburg,  abstracted  from  an  article  by  Dr. 
E.  Schumann  in  Archiv.  fur  Klinische  Chirurgie,  1907,  Band  84,  page 
860. 

Case  XXVIII.  — X-ray  operator;  cracks  and  fissures  of  fingers  and  on 
dorsum  of  hands,  which  were  excessively  painful  and  did  not  yield  to  any 
conservative  treatment.  These  warty  growths  of  epithelium  were  finally 
excised  and  sutured.  Unna  examined  the  specimens  and  pronounced 
them  as  beginning  epitheliomata.  The  tissue  was  so  friable  that  the 
sutures  did  not  hold,  and  it  was  difl^cult  to  make  satisfactory  sections. 
The  wounds  healed  by  second  intention   and  remained  well  thereafter. 

Case  XXIX.  —  Patient,  X-ray  tube  maker.  Usual  pigmentations  of 
the  skin  of  face  and  arms;  typical  changes  of  finger  nails.  In  addition, 
two  prominent  keratotic  growths  on  the  back  of  one  hand.  These  were 
excised  and  pronounced  by  Dr.  Fraenkel  to  be  epidermoid  carcinoma. 

Case  XXX.  —  Young  physician;  severe  lesions  on  fingers  and  backs  of 
hands.  On  the  right  forefinger  a  chronic  paronychia,  and  on  the  back  of 
the  hand  a  small  ulceration.  Usual  treatment  without  avail.  The  pain 
was  extreme,  often  keeping  the  patient  awake  all  night.     Evulsion  of  the 


396  PORTER. 

nail  was  not  beneficial.  The  terminal  phalanx  was  amputated  and  the 
ulcer  excised  and  skin  grafted.  The  graft  died,  but  satisfactory  healing 
took  place  eventually.  Pathological  examination  showed  typical  skin 
cancer. 

Case  XXXI.  —  Man,  32  years,  who  after  three  years  of  X-ray  work 
suflFered  from  severe  lesions  on  both  arms,  breast,  neck,  and  face.  In  1901 
there  began  a  slowly  growing  ulceration  of  the  back  of  the  right  hand? 
which  by  the  middle  of  1902  had  become  a  gangrenous  epithelioma; 
glands  enlarged  at  the  elbow  and  in  the  axilla.  Amputation  at  the 
shoulder ;  axillary  glands  removed,  and  found  full  of  squamous  celled 
carcinoma.  Sound  healing.  In  December,  1904,  a  typical  cancer  of  the 
lower  lip  and  another  of  the  angle  of  the  mouth  were  excised,  as  was  a 
suspicious  lesion  on  the  back  of  the  left  hand.  In  March,  1905,  a  growth 
of  the  cheek  was  removed,  which  was  pronounced  by  Unna  to  be  a 
sarcoma.  In  September,  1905,  excision  of  the  right  lower  jaw  for  carci- 
noma. Recurrence  involving  the  tongue  and  the  adjacent  cheek  was 
present  in  February,  1906.     Death  soon  followed. 

Case  XXXII.  —  Patient  operated  upon  by  Professor  Trendelenburg. 
The  specimen  was  carefully  studied  by  Dr.  Schumann.  Man,  39  years ; 
unusually  exposed  since  1896  to  the  X-rays  —  he  used  his  own  hands  to 
test  the  tubes  —  four  years  later,  developed  a  dermatitis  of  both  hands. 
The  skin  became  rigid,  dry,  and  swollen ;  the  nails  brittle  with  chronic 
onychia.  This  condition  lasted  two  years.  In  1902  he  became  worse. 
On  the  right  hand  there  developed  yellowish,  horny  growths,  particularly 
over  the  knuckle  of  the  third  finger.  In  1906  the  removal  of  this  keratosis 
left  behind  an  ulcer,  which  in  two  months  grew  to  the  size  of  a  mark  piece 
with  indurated  edges.  The  epitrochlear  glands  were  enlarged  ;  the  axillary 
glands  not  palpable.  In  February,  1907,  the  ulcer  was  radically  excised 
and  skin  grafted;  healing  uncomplicated.  No  mention  is  made  of  the 
treatment  of  the  enlarged  epitrochlear  glands.  Examination  of  the  ulcer 
showed  typical  epidermoid  cancer. 

Cases  XXXIIL,  XXXIV.,  XXXV.,  XXXVI.,  XXXVII.— The  fol- 
lowing cases  occurring  in  Great  Britain  are  abstracted  from  a  paper  by 
Mr.  Foulterton  in  the  Transactions  of  the  Pathological  Society,  July, 
1906,  and  from  personal  communication  from  Dr.  Cecil  W.  Rowntree,  and 
a  paper  by  him,  published  in  the  Archives  of  the  Middlesex  Hospital, 
Volume  XIII.,  July,  1908. 

Case  XXXIII.  —X-ray  work  in  1897,  at  the  age  of  38.  In  two  years, 
loss  of  tactile  sensation  in  fingers.  In  May,  1903,  severe  dermatitis. 
Resulting  ulcers  took  four  months  to  heal.  Warty  bodies  next  developed 
on  the  dorsal  aspect  of  index  and  second  fingers.  A  similar  acute  attack 
in  December,  1903.  An  ulcer  on  the  index  finger  refused  to  heal  and 
increased  in  area  and  depth  ;  in  September,  1904,  the  finger  was  ampu- 
tated. In  1906,  a  small  superficial  ulcer  on  the  middle  phalanx  of  the 
middle  finger  persisted,  and  was  excised  and   grafted.     Examination  of 


SURGICAL   TREATMENT   OF   X-RAY   CARCINOMA.         397 

the  ulceration,  for  which  amputation  was  done,  showed  a  typical  epithe- 
lioma with  cell-nest  formation,  which  invaded  the  underlying  bone.  Exam- 
ination of  the  ulcer  excised  in  1906  shows  absence  of  elastic  tissue, 
thickening  of  the  epithelium,  early  keratinization  and  plasma  cell  infil- 
tration ;  a  precancerous  condition. 

Case  XXXIV.  — Man,  60  years  ;  engaged  for  some  years  in  the  manu- 
facture of  X-ray  tubes.  For  painful  fissure  over  the  last  interphalangeal 
joint  of  the  first  finger,  excision  was  performed.  Microscopic  examination 
showed  early  but  undoubted  squamous  cell  carcinoma. 

Case  XXXV.  —  Man,  40  years.  The  third  finger  showed  a  glossy 
appearance  of  the  skin,  which  was  thin  and  adherent  to  the  underlying 
structures.  The  nail  had  entirely  disappeared,  except  for  a  small  portion 
at  one  edge.  There  were  no  cracks  nor  warts,  nor  any  actual  ulceration 
anywhere,  but  at  the  base  of  the  finger  was  an  area  where  the  surface 
epithelium  showed  a  slight  irregularity.  This  finger  was  amputated  at 
the  metacarpo  phalangeal  joint,  and  the  metacarpal  bone  subsequently 
dissected  out.  Examination  of  the  indurated  skin  showed  the  presence 
of  a  malignant  growth,  infiltrating  the  deeper  structures ;  a  typical  squa- 
mous cell  carcinoma,  with  well-marked  cell-nest  formation.  The  axilla 
was  cleaned  out,  but  the  enlarged  glands  showed  no  evidence  of 
metastases. 

Case  XXXVI.  —  Man,  42  years  ;  engaged  for  several  years  in  the  manu- 
facture of  X-ray  apparatus.  For  two  years  the  left  hand  had  been 
affected,  and  eighteen  months  previously  a  growth  had  appeared  on  the 
middle  finger ;  surgical  treatment  had  been  refused.  Finally  the  left 
middle  finger  became  very  greatly  enlarged  by  an  irregularly  lobed  new 
growth,  which  was  ulcerating  on  the  surface  and  very  foul.  There  were 
a  number  of  irregular,  pigmented  warts ;  no  enlarged  glands.  The  finger 
was  amputated  through  the  proximal  end  of  the  shaft  of  the  third  meta- 
carpal bone;  good  recovery.  Since  this  operation  in  1905  there  has 
been  no  evidence  of  recurrence  in  the  hand,  but  there  are  persistent 
ulcerations  upon  the  chin  and  over  the  upper  part  of  the  sternum. 
Microscopic  examination  of  the  growth  shows  that  it  is  composed  of 
small  and  slender  columns  of  eyelets  of  squamous  cells,  irregularly  dis- 
tributed and  separated  from  one  another  by  a  well-marked  connective 
tissue  stroma,  composed  of  large  cells  with  large  nuclei.  Mitotic  figures 
are  present.  "  Of  special  interest  in  this  ulceration  is  the  striking 
appearance  of  the  connective  tissue  stroma,  the  individual  cells  being  of 
a  size  and  character  not  usually  met  with.  Their  large  size  and  great 
number  produce  the  appearance  as  if  the  small  eyelets  of  epithelial  cells 
were  dispersed  throughout  granulation  tissue,  and  suggesting  the  view 
that  the  connective  tissue  cells  themselves  are  endowed  in  these  instances 
with  a  special  activity.'"  None  of  the  cells  were  found  to  be  multinu- 
cleated. An  X-ray  of  the  finger  removed  showed  a  total  disappearance  of 
the  bony  tissue  of  the  first  and  second  phalanges  and  suggested  further 
study  by  the  X-rays  of  such  hands.  In  other  instances,  also,  marked 
atrophy  of  the  bony  tissue  was  noted,  and  in  one  case  absorption  had 


398  PORTER. 

taken  place,  giving  tlie  appearance  of  a  punched-out  area  in  the  middle 
phalanx. 

Case  XXXVII.  —  Man,  38  years;  seen  in  July,  1905.  Had  been  work- 
ing with  the  X-rays  for  six  years.  On  account  of  trouble  with  his  hand 
gave  up  work  in  1902.  The  skin  of  both  hands  was  thin,  glossy,  and 
pigmented;  usual  telangiectases.  On  the  proximal  phalanx  of  the  right 
middle  finger  was  a  growing  ulcer  about  one  inch  in  diameter.  There 
were  two  other  smaller  ulcers,  which  showed  no  evidence  of  healing.  Xo 
enlargement  of  glands.  The  finger  was  amputated  with  nearly  the  whole 
metacarpal  bone,  and  the  ulcer  over  it.  The  other  ulcer  was  excised 
and  grafted.  Patient  remained  well  for  a  year,  when  a  small  ulcer 
appeared  in  the  scar;  this  healed,  however,  eventually.  A  few  months 
later  a  scab  formed  over  the  scar,  which  was  gradually  raised  by  a 
prominent  growth  about  the  size  of  half  a  cherry,  which  rose  dome-like 
above  the  skin.  This  growth  was  bright  red  in  color  :  of  firm  consistenc}'. 
It  was  removed,  and  the  resulting  wound  covered  with  a  Thiersch  graft. 
At  present,  May,  1908,  there  is  no  recurrence.  Microscopic  section  of 
the  original  ulcer  revealed  a  keratinization  and  a  squamous  cell  carcinoma, 
in  which  the  cell  nests  are  numerous  and  well  developed.  Examination 
of  the  second  growth  showed  that  it  consisted  entirely  of  young  granula- 
tion tissue,  which  replaced  the  epidermis  and  corium  for  a  limited  area, 
the  epidermis  gradually  merging  into  and  disappeanng  in  the  granula- 
tion tissue.  "The  cells  composing  the  granulation  tissue  are  unusually 
large  and  well  developed,  and  possess  large,  round,  oval  nuclei,  contain- 
ing much  chromatin  and  staining  deeply ;  in  fact  the  appearance  of  these 
cells  are  strikingly  similar  to  that  of  the  cells  which  formed  the  stroma  of 
the  new  growth  in  the  previous  case.  The  elastic  tissue  is  disappearing 
in  a  narrow  zone  below  the  epithelium  with  moderate  plasma  cell  infil- 
tration. 

Sujnniary ;  Five  cases  of  carcinoma,  developing  with  a  long  latent 
period,  in  cases  of  chronic  X-ray  dermatitis.  In  all  but  one,  early  opera- 
tion. One  case  neglected,  but  no  involvement  found  in  the  axillary  glands. 
In  two  instances,  attention  is  called  to  an  unusual  form  of  granulation 
tissue  in  which  the  cells  are  unusually  large  and  contain  large,  round,  or 
oval  nuclei,  and  stain  deeply. 

Case  XXXVIII.  —  H.  E.  (physician);  amputation  of  arm  for  epithe- 
lioma of  hand. 

Case  XXXIX.  —  At  Leeds,  England;  amputation  of  arm  for  car- 
cinoma. 

Fatal  cases,  X-ray  carcinoma. 

Case  XL.  —  B.  (physician),  England;  X-ray  carcinoma  of  hands; 
general  metastases  and  death. 


SURGICAL   TREATMENT    OF    X-RAY    CARCINOMA.  399 

Case  XLI.  —  W.  C.  E.  (physician).  Personal  communication  from 
Dr.  Nevins  Hyde  of  Chicago.  X-ray  cancer  of  hand;  general  metastases 
and  death. 

Case  XLII.  —  W.  (physician),  Rochester,  N.Y.  Personal  com- 
munication from  Dr.  W.  B.  Coley  of  New  York.  For  five  years,  had 
been  using  X-rays  continuously.  Ulcerations  present  for  six  months  on 
the  backs  of  both  hands,  specimens  from  which  were  examined  by  Pro- 
fessor Welch  of  Johns  Hopkins  Hospital  and  found  to  be  undoubted 
epithelioma.  The  carcinoma  had  deeply  involved  the  metacarpal  bones 
of  the  index  and  middle  fingers.  Amputation  of  right  hand  above  wrist, 
and  thorough  excision  of  ulceration  on  the  left  hand,  Oct.  10,  1904 
Subsequent  recurrence  in  axilla  and  liver;  death. 

Case  XLHI. — C.  D.  Personal  communication  from  Dr.  Samuel 
Lloyd  of  New  York  and  Dr.  W.  B.  Graves  of  East  Orange,  N.  J.  This 
patient  was  very  seriously  burned  on  both  hands  years  before  in  working 
with  X-ray  tubes.  He  was  treated  at  many  different  hospitals.  Skin 
grafting  was  tried  without  result,  until  finally' epithelioma  developed  on 
the  right  hand  and  on  the  base  of  the  little  finger  of  the  left  hand.  At 
the  time  of  Dr.  Lloyd's  first  examination  the  right  hand  was  infiltrated 
with  carcinoma  and  the  axillary  glands  were  involved.  The  arm  was 
amputated  at  the  shoulder  joint,  and  the  glands  above  and  below  the 
clavicle  removed.  Amputation  of  the  left  hand  was  advised  but  refused. 
This  was  Aug.  8,  1902.  The  ulceration  gradually  increased  in  size  and 
depth  and  the  left  a.rm  was  amputated  by  Dr.  Graves  on  March  16,  1904. 
Death  followed  from  mediastinal  recurrence  in  October,  1904. 

Case  XLIV. —  B.  F.  (female),  of  San  Francisco,  Cal,  Personal 
communication  from  Dr  Childs  Macdonald.  Patient  was  a  pioneer  in 
X-ray  work.  In  1903  her  hands  commenced  to  show  signs  of  X-ray  der- 
matitis, the  nature  of  which  was  not  understood,  and  attributed  to  chem- 
icals used  in  developing  the  plates.  Patient  worked  twelve  hours  a  day, 
without  protection.  In  the  early  part  of  1904  she  came  for  the  first 
time  under  treatment  The  fingers  of  both  hands  were  badly  ulcerated  ; 
chiefly  the  tissues  over  the  middle  phalanges  and  the  middle  joints ;  all 
the  nails  were  affected,  the  surfaces  presenting  ulcerated,  warty  condition, 
the  warts  assuming  the  form  of  necrogenica,  healing  alternating  with 
ulceration.  All  the  secreting  glands  and  hair  follicles  were  destroyed,  so 
that  the  skin  was  hard  and  dry,  and  cracked  easily.  All  sorts  of  treatment 
of  ointments  and  washes  were  without  permanent  benefit.  In  November, 
1904,  a  wart  appeared  on  the  index  finger,  near  the  terminal  phalanx, 
which  was  very  raw,  and  grew  with  great  rapidity.  A  portion  was  removed, 
under  cocaine,  and  submitted  to  Dr.  Rifkogel,  who  reported  a  branching 
papilloma,  with  a  tendency  to  downward  growth,  and  advised  amputation. 
This  the  patient  refused,  so  the  growth  was  freely  excised  and  healed 
healthily.     A  few  weeks  afterwards,  however,  a  nodule  appeared  near  the 


400  PORTER. 

scar,  which  pushed  up  through  the  epithelium,  broke  through  it  and 
appeared  exactly  the  same  as  growth  No.  i.  The  glands  in  the  axilla 
were  found  somewhat  enlarged.  Radical  operation  was  again  refused, 
until  after  Christmas,  when  axilla  was  freely  opened  and  the  whole  space 
cleared  of  glands.  Pathological  examination  of  these  showed  undoubted 
involvement  with  epidermoid  carcinoma.  In  the  course  of  a  week,  more 
nodules  appeared  just  below  the  acromioclavicular  articulation.  It  was 
decided  that  the  only  chance  of  recovery  lay  in  amputation  at  the  shoulder. 
Accordingly  on  Jan  27,  1905,  after  preliminary  ligation  of  the  subclavian 
in  the  third  part,  the  arm  and  scapula  with  the  clavicle  were  removed. 
The  patient  rallied  well  from  the  operation,  and  the  wound  healed  rapidly, 
but  about  the  end  of  April,  1905,  a  recurrence  took  place  at  a  point  rep- 
resenting the  position  of  the  inferior  angle  of  the  removed  scapula.  This 
was  excised  and  found  to  be  carcinoma.  Slowly,  and  then  rapidly,  other 
nodules  appeared,  until  ultimately  the  whole  of  the  vertical  scar,  corre- 
sponding to  the  vertebral  border  of  the  scapula,  became  involved.  Metas- 
tases took  place  in  the  pleura  and  lungs,  and  the  patient  died  on  Aug.  3, 

1905- 

On  reading  this  history  it  is  obvious  that  the  patient  by  refusing  early 
radical  surgical  treatment  jeopardized  her  life,  though  it  is  of  course 
possible  that  metastases  had  occurred  early. 

Case  XLV.  —  F.  (physician).  Personal  communication  from  Dr  L.  L. 
McArthur  of  Chicago,  dated  April  26,  1907.  Patient  was  the  first  photog- 
rapher to  develop  X-ray  plates  in  America.  "  He  early  developed  the 
chapped  and  fissured  hands  which  go  with  the  exposure  to  the  ray,  espe- 
cially in  those  who  combined  the  development  of  their  plates  with  their 
X-ray  work.  For  the  last  three  years  he  has  been  having,  from  time  to  time, 
minor  surgical  procedures  in  the  way  of  removal  of  a  phalanx  now  and 
then,  until  three  fingers  of  the  right  hand  and  two  on  the  left  had  been 
sacrificed.  After  various  plans  of  local  treatment  and  a  trip  to  Europe 
in  search  of  remedial  agents,  he  came  to  me  for  the  first  time  with  an 
enormous  axillary  involvement.  This  was  indubitably  squamous  celled 
carcinoma.  The  radical  operation  with  removal  of  portions  of  the  pecto- 
rales  and  a  dissection  of  the  axilla  en  bloc  failed  to  effect  an  arrest  of  the 
trouble.  Recurrence  took  place  very  promptly,  and  within  three  months 
again  filled  the  axilla,  and  involved  the  supraclavicular  glands.  Deeming 
it  hopeless  to  subject  him  to  further  surgical  interference,  trypsin  injec- 
tions were  given,  with  a  resulting  liquefaction  of  the  axillary  mass  to  a 
nonpurulent,  sero-sanguinolent  fluid,  containing  immense  masses  of  epithe- 
lial cellular  detritus,  as  was  shown  on  opening  and  draining  the  same. 
After  lingering  for  six  weeks  he  finally  succumbed  to  a  multiple  metastasis 
on  April  23,  1907. 

Case  XLVI.  —  R.  V.  W.  (physician);  X-ray  machine  manufacturer; 
has  used  both  static  and  coil  machines  continuously  from  their  beginning, 
subjecting  himself  to  countless  fluoroscope  examinations.     His  skin,  both 


SURGICAL   TREATMENT   OF   X-RAY   CARCINOMA.         4OI 

front  and  back,  for  a  number  of  years,  has  been  covered  with  characteristic 
lesions,  many  of  which  have  recently  become  epitheliomata.  He  was 
operated  upon  for  a  carcinoma  of  the  cheek,  by  the  actual  cautery,  down 
to  the  mucous  membrane,  and  a  thorough  removal  of  epitheliomatous 
glands  on  both  sides  of  the  neck.  He  had  also  epitheliomata  of  both 
hands  and  some  on  the  back.  Patient  died  in  April,  igo8,  of  extensive 
metastatic  carcinoma  of  the  liver. 

Case  XLVH. — J.  B.  Personal  communication  from  Dr.  Russell  S. 
Fowler  and  his  house  surgeon,  Dr.  C.  H.  Criley,  of  the  Brooklyn  Hospi- 
tal, New  York.  Man,  33  years;  a  glass  worker  by  occupation,  since  the 
age  of  fourteen.  Soon  after  the  discovery  of  the  X-ray,  patient  became 
interested  in  the  manufacture  of  the  tubes.  His  work  was  chiefly  in  the 
testing-room,  where  he  worked  over  a  bench,  waist  high  exposed  for  one 
to  four  hours  a  day.  In  1900  he  noticed  a  few  small,  warty  growths  on 
the  fingers,  knuckles,  and  backs  of  hands.  In  1904  patient  gave  up 
business  on  account  of  general  poor  health,  at  which  time  he  noticed  a 
peculiar  erythem.a  with  a  slight  tendency  toward  hard,  warty  nodules  over 
the  face,  neck,  and  anterior  trunk,  above  the  waist  line.  The  keratoses 
were  still  very  small,  the  largest  not  more  than  a  quarter  of  an  inch  in 
diameter.  He  has  some  on  the  face  removed  with  the  actual  cautery  and 
silver  nitrate.  The  growths  rapidly  recurred  and  increased  in  size,  becom- 
ing soft  and  slightly  ulcerated. 

Examination,  April  19,  1907.  Marked  erythema  and  mottling  of  the 
skin  of  face,  trunk,  and  arms.  Many  scattered,  hard,  flat  papules.  A 
small  cutaneous  horn  on  the  forehead  and  several  smaller  ones  on  the 
chest.  Large  epithelioma  over  the  metatarso  phalangeal  joints  of  index 
and  middle  fingers  of  left  hand.  Deep  ulceration  and  small  ulcerations 
over  some  of  the  joints  of  the  right  hand. 

Operation :  amputation  of  first  and  second  fingers  with  heads  of  meta- 
carpal bones  of  left  hand.  Removal  of  numerous  epitheliomata.  Patient 
refused  more  radical  treatment  and  would  only  allow  curetting  of  the 
carcinomata  on  the  right  hand. 

Nov.  II,  1907.  The  growths  on  the  right  hand  had  increased  in  size 
and  fused,  but  were  not  deep.  Rapid  recurrence  at  site  of  amputation  of 
fingers  of  left  hand  ;  only  curettage  was  permitted,  followed  by  an  unsuc- 
cessful attempt  at  skin  grafting. 

March  11,  1908.  Since  last  examination,  rapid  progress  of  the  disease, 
involving  the  base  of  the  thumb  and  the  metatarsal  bones  of  the  third 
and  fourth  fingers  ;  no  evidences  of  glandular  enlargement.  Amputation 
at  junction  of  middle  and  lower  thirds  of  left  forearm  ;  amputation  healed 
by  primary  union.     Another  curettage  of  the  right  hand. 

April  20,  1908.  Another  attempt  was  made  to  benefit  right  hand  by 
curettage  and  skin  grafting ;  unsuccessful.  Discharged  on  June  14,  with 
cancer  slowly  spreading  on  right  hand.  No  evidence  of  granular  enlarge- 
ment anywhere.  By  Aug.  8,  1908,  however,  the  general  condition  had 
become  poor,  with  marked  loss  of  weight;  epitrochlear  and  axillary  lymph 


402  PORTER. 

nodes  on  the  left  enlarged;  no  recurrence  in  stump.  Epithelioma  of 
right  hand  had  begun  to  spread  rapidly,  and  had  involved  deeply  the 
metacarpo  phalangeal  areas  of  the  first  and  second  fingers.  These  fingers 
were  accordingly  amputated  on  August  ii,and  the  wound  skin  grafted. 
The  left  epitrochlear  and  axillary  glands  increased  very  rapidly  in  size, 
forming  great  masses  which  were  extremely  painful.  On  Sept.  25,  1908, 
interscapulo  thoracic  amputation  was  performed,  and  a  small  epithelioma- 
tous  ulcer  removed  in  the  region  of  the  umbilicus.  The  amputation 
wound  healed  very  slowly,  showing  evidence  of  recurrence.  Patient  died 
Nov.  7,  1908,  of  general  carcinosis. 

Pathological  report.  Glands  above  clavicle  carcinomatous.  The  lymph 
nodes  in  the  mediastinum  and  about  the  bronchi  were  enlarged  to  about 
the  size  of  a  fist.  There  were  nodules  in  both  the  parietal  and  visceral 
layers  of  each  pleura.  Some  nodules  in  both  lungs.  Nodules  also  in 
kidneys  and  adrenals.  Numerous  carcinomatous  areas  in  the  liver  and 
one  in  the  wall  of  the  stomach. 

SiDiiinary  I  In  1897  began  work  with  the  X-rays,  testing  the  tubes  for 
several  hours  a  day.  First  noticed  erythema  and  warty  growths  in  1900. 
In  1905,  keratoses  and  warts  had  formed  on  both  hands,  chest,  and  face. 
First  carcinoma  developed  and  required  amputation  of  two  fingers  of  the 
left  hand  in  April,  1907;  similar  growth  curetted  on  right  hand.  By 
March,  1908,  rapid  extension  of  the  disease  necessitating  amputation  of 
left  forearm;  curettage  of  epithelioma  on  right  hand.  August,  1908, 
involvement  of  epitrochlear  and  axillary  glands.  Aug.  11,  1908,  ampu- 
tation of  fingers  of  right  hand.  Sept.  25,  1908,  amputation  at  shoulder. 
Death  on  Nov.  7,  1908  ;  general  carcinosis. 

On  reading  this  history  it  is  obvious  that  death  was  caused  by  the 
patient's  refusal  to  subject  himself  to  early  and  radical  operation.  The 
amputation  at  the  shoulder  was  not  performed  until  after  general  metas- 
tases had  taken  place. 

While  on  reading  the  histories  of  these  cases  one  cannot 
fail  to  be  struck  by  the  inevitable  and  progressive  evolution 
of  the  disease  from  the  milder  grades  of  inflammation  to 
ultimate  carcinomatous  degeneration,  there  appear,  fortu- 
nately, a  few  exceptions  to  the  general  rule,  which  careful 
inquiry  from  my  own  and  other  cases  have  developed  ;  where 
through  the  years,  in  spite  of  persistent  lesions,  there  has 
been  a  gradual  improvement  in  the  general  condition  of  the 
hands,  as  if  the  natural  reparative  power  of  the  skin  had 
begun  to  assert  itself.  This  is  analogous  to  a  few  recent 
cases  of  improvement  in  the  genital  glands,  after  protracted 
loss  or  abeyance  of  function.  The  degree  to  which  this 
return  toward   normal   may  develop   must  depend   upon  the 


SURGICAL   TREATMENT   OF   X-RAY    CARCINOMA.         403 

presence  or  absence  of  continued  irritations,  and  the  depth 
or  degree  of  the  original  damage  to  the  skin  and  subcuta- 
neous tissues. 

Pain.  —  The  amount  of  pain  which  these  patients  suffer  is 
variable,  though  usually  extreme.  From  my  experience  and 
personal  communications  from  patients  I  believe  that  the 
agony  of  inflamed  X-ray  lesions  is  almost  unequalled  by  any 
other  disease.  Its  character  has  been  described,  and  varies 
with  individuals.  While  morphia  has  been  used  in  some  of 
the  cases,  it  is  really  surprising  to  find  how  man}'  have  borne 
their  pain  without  resorting  to  its  habitual  use.  The  pain 
seems  to  be  due,  in  some  instances,  to  the  exposure  of 
irritated  nerve  endings  in  a  raw  ulcer,  like  the  "  erethystic  " 
varicose  ulcer  of  the  leg,  to  suppurating  nail  beds,  irritated 
by  small  pieces  of  nail,  and,  in  acute  burns,  very  probably 
to  a  definite  neuritis.  In  the  more  chronic  cases  I  believe 
that  the  microscopic  sections  show  quite  clearly  that  the  pain 
is  caused  by  the  cicatricial  contraction  in  the  thickened  corium, 
compressing  the  nerves.  In  one  case  of  mine  (XIX.) 
the  nerves  were  shown  to  be  actually  involved  in  an  infil- 
trating cancer.  At  another  time,  the  lateral  digital  nerve  of 
the  little  finger  was  exposed  at  the  base  of  a  slowly-healing 
sore  ;  sensitiveness  and  pain  were  intolerable,  but  ceased  as 
soon  as  the  bare  nerve  was  covered  with  granulation  tissue 
and  skin.  Without  regard  to  the  particular  cause  of  the 
pain,  in  either  the  acute  or  chronic  cases,  adequate  excision 
of  the  lesions  has  invariably  given  immediate  relief.  In 
Cases  IV.  and  XV.,  though  dirtering  so  far  as  one  could  see 
in  no  respect  from  other  very  painful  ulcerations,  pain  was 
remarkable  for  its  absence  throughout  the  whole  course  of 
the  disease.  Rupture  of  the  dilated  capillaries  is  of  frequent 
occurrence  and  always  accompanied  by  extreme,  radiating 
pain,  until  the  extravasation  works  to  the  surface,  forms  a 
black  spot,  and  is  thrown  off"  in  the  process  of  desquamation, 
when  the  pain  ceases.  Not  infrequently,  these  minute 
hemorrhages  form  the  sites  of  subsequent  ulcerations. 

Acute  infections  arising  in  the  fissures  or  inflamed  nail 
beds,    keratoses    or    ulcerations,    or    coincident    injuries   are 


404  PORTER. 

responsible  for  much  of  the  disability  associated  with  such 
hands,  always  rendering  more  painful  lesions  which  were 
painful  enough  before. 

The  palliative  treatment  of  these  chronic  X-ray  lesions 
must  be  left  in  a  great  measure  to  the  personal  experience 
of  the  individual.  Relief  from  pain  and  improvement  often 
take  place  under  remedies  which  in  another  patient  are  most 
painful  and  harmful.  In  general,  dry  treatment,  when  it 
can  be  borne,  combined  with  protection  has  seemed  to  be 
most  beneficial.  Maceration  should  be  avoided.  Pure  ben- 
zoinated  lard  I  have  found  the  most  valuable  ointment; 
ichthyol  combined  with  lanolin  occasionally  useful.  At 
times,  local  anesthetics  must  be  used;  preferably  a  weak 
solution  of  cocaine  upon  two  layers  of  compress  cloth. 
Orthoform  I  am  convinced  should  never  be  used,  owing  to 
its  tendency  to  produce  ulcerations.  Of  the  washes,  simple 
salt  solution  or  aluminum  acetate  are  valuable.  If  infec- 
tion is  present,  citrate  of  silver  (i-6,000)  has  been  very 
useful  in  most  of  my  cases.  Alumnol  (1-200)  has  proved  a 
most  satisfactory  antiseptic  and  astringent.  The  keratoses 
may  be  softened  with  a  solution  of  caustic  soda  and  shaved 
down  with  a  sharp  knife  or  pumice  stone.  If  they  are 
scratched  off,  bleeding  is  profuse,  and  ulceration  not  rare. 
The  actual  cautery  which  several  have  used,  while  tempo- 
rarily destroying  the  condition,  seems  to  invite  recurrence 
on  a  larger  scale.  Sparking  with  high  tension  current  has 
been  tried  by  various  radiographers  with  temporary  improve- 
ment, but  no  permanent  benefit.  With  the  non-surgical 
methods  of  destroying  keratoses,  I  have  had  no  personal 
experience,  Dr.  Whitehouse  of  New  York  prefers  liquid  air, 
while  Dr.  Pusey  of  Chicago  is  well  satisfied  with  carbon 
dioxide  snow.  Both  of  these  milder  methods  have  the 
advantage  over  excision  of  causing  no  detention  from  busi- 
ness, and  possibly  of  acting  only  upon  the  abnormal  cells, 
without  affecting  normal  tissues. 

After  months  or  years  of  treatment,  or  neglect  of  treat- 
ment, carried  out  with  more  or  less  relief  upon  various  lines, 
the  early  X-ray  worker  usually  finds  that  while  the  general 


SURGICAL   TREATMENT    OF    X-RAY    CARCINOMA.         405 

condition  of  the  hands  may  have  improved  somewhat,  either 
certain  keratoses  recur  after  removal,  or  the  nail  beds  are 
afifected,  or  that  after  healing  and  breaking  down  several 
times  a  particular  ulceration  finally  refuses  to  heal.  The 
lesions  are  chronic,  moderately  severe,  recurring,  eventually 
persistent.  The  first  question  usually  asked  is,  "  Should 
X-ray  work  be  given  up?  "  While  it  is  obvious  that  to  do 
this  would  be  conservative,  I  feel  personally  convinced  that 
no  harm  results  from  X-ray  work  carried  out  with  all  modern 
precautions.  It  is  easy  to  give  this  advice,  but  only  in 
exceptional  instances  is  the  advice  conscientiously  carried  out. 
The  second  question,  "What  is  the  danger  of  cancer?" 
Provided  ulcerations  have  not  persisted  for  more  than  three 
months,  or  have  not  occurred  at  the  site  of  an  inflamed 
keratosis,  I  believe  it  to  be  slight. 

The  surgical  treatment  of  X-ray  lesions. — Acute  and 
sub-acute  burns  :  By  this  I  mean  the  results  of  one  or  at  the 
most  a  few  protracted  exposures  such  as  occurred  in  Case 
II.  The  severe  symptoms  develop  from  a  few  hours  to  a 
few  weeks  after  the  injury,  and  are  accompanied  by  extreme 
pain.  The  area  apparently  involved  gradually  shrinks, 
leaving  behind,  eventually,  evidence  of  the  actual  damage 
done.  Depending  upon  the  depth  of  the  lesion  there  is 
desquamation,  blistering,  ulceration,  or  deeper  death  of  the 
tissues.  In  all  degrees  we  have  the  abundant  formation  of  a 
very  tough  and  adherent  fibrin  with  great  pain  upon  its 
removal ;  this  condition  is  well  shown  in  Case  VIII.,  and  is 
peculiar  to  X-ray  lesions.  For  a  time,  at  least,  the  deterio- 
rated tissues  seem  to  be  in  unstable  equilibrium,  unable  to 
slough  or  to  repair  themselves.  Pain  is  extreme  and  for  its 
relief  the  tendency  is  to  perform  an  early  excision,  but  it  is 
most  difficult  to  determine  how  much  tissue  should  be 
excised.  While  in  Case  II.  immediate  relief  of  the  pain 
followed  operation,  and  the  excision  at  the  time  seemed 
adequate,  the  wound  failed  to  heal  and  further  necrosis 
occurred  in  the  margins  and  base  of  the  wound.  In  general, 
then,    except    for    the     pain,    I    would    advise     conservative 


406  PORTER. 

treatment  of  these  acute  or  sub-acute  lesions  until  what  would 
correspond  to  a  "  line  of  demarcation  "  has  been  established. 
Excision  with  skin  grafting  should  be  preferred  to  plastic 
operations.  If  the  graft  fails  to  grow  owing  to  continued 
necrosis,  later  grafting  may  be  done  after  the  wound  has  ' 
granulated. 

Fissures  and  thin  skin  over  the  knuckles.  —  The  treatment, 
whether  conservative  or  operative,  must  depend  upon  the 
individual  experience  of  the  operator  and  the  choice  of  the 
patient.  If  skin  grafting  is  successful,  there  can  be  no  doubt 
that  the  result  will  be  most  satisfactory,  and  to  my  mind 
should  be  advised. 

Keratoses. — Until  recently,  my  personal  experience  led 
me  to  believe  that  simple,  uninflamed,  non-ulcerating  kera- 
toses were  benign,  but  I  am  now  convinced  that  there  are 
exceptions,  and  that  all  keratoses  which  show  a  tendency  to 
dip  below  the  level  of  the  surrounding  skin  should  be 
regarded  as  suspicious.  Microscopical  examination  of  many 
of  those  which  I  have  removed  showed  all  stages  from  a 
perfectly  harmless  condition  to  beginning  invasion  of  the 
corium.  I  have  had  no  experience  with  liquid  air  or  carbon 
dioxide  snow,  but  have  found  their  removal  by  operation 
very  satisfactory.  If  situated  upon  the  dorsum  of  the  hand 
where  the  skin  is  lax,  excision  and  suture  is  satisfactory. 
If  upon  the  fingers,  especially  over  the  knuckles,  excision 
and  skin  grafting  should  be  practised.  If  superficial, 
excisions  well  into  the  corium  will  be  adequate  when  a  thin 
Thiersch  graft  can  be  applied.  If  primary  grafting  fails,  I 
am  convinced  from  several  observations  that  thorough 
removal  of  the  diseased  tissue  promotes  spontaneous  healing 
from  the  edges.  It  has  been  suggested  that  the  irritation  of 
the  graft  excites  the  surrounding  skin  to  the  formation  of 
thickened  epithelium,  but  it  has  seemed  to  me  that  if 
recurrence  of  the  keratoses  takes  place  at  .the  margins  of  the 
graft  that  this  is   more  reasonably  explained  by  inadequate 


SURGICAL   TREATMENT   OF   X-RAY    CARCINOMA.         407 

excision.     If  the  keratosis  suggests  malignancy,   the  whole 
thickness  of  the  skin  should  certainly  be  removed. 

Pachydermia  with  telangiectasis.  —  The  proper  treatment  of 
this  condition  is  extremely  difficult  to  determine.  In  Case 
XV.,  where  the  whole  front  of  the  chest  was  affected,  and  in 
VIII.  where  the  anterior  abdominal  wall  was  in  a  similar  con- 
dition, with  undoubted  epithelioma  in  certain  unsuspicious 
localities,  treatment  must  depend  upon  the  individual  indica- 
tions. In  a  case  like  XV.  the  patient  must  be  watched  with 
care;  in  one  like  Case  VIII.  it  soon  became  obvious  that  all 
of  the  damaged  tissues  would  gradually  slough  unless 
removed  by  operation.  The  histological  examination  of  such 
tissue  shows  that  the  main  arteries  are  pervious,  but  that 
there  is  both  marked  endarteritis  and  endophlebitis,  which 
unless  collateral  circulation  is  formed  will  probably  lead  to 
subsequent  anemic  necrosis. 

Paronychia  and  onychia.  —  Probably  the  most  painful  of 
the  X-ray  lesions,  and  one  of  the  most  persistent.  If  disin- 
fection and  dry  treatment  does  not  bring  about  healing  in  a 
reasonable  length  of  time,  extirpation  of  the  nail  is  clearly 
indicated.  If  healing  then  does  not  take  place,  the  whole 
nail  bed,  both  at  the  base  and  on  the  sides  should  be 
destroyed.  Owing  to  the  difficulty  of  distinguishing  between 
nail-forming  membrane  and  the  insertion  of  the  extensor 
tendon  into  the  terminal  phalanges,  subsequent  re-formation 
of  portions  of  the  nail  is  not  uncommon.  Amputation  with 
certain  cure  is  often  too  long  delayed  in  this  condition. 

Ulcers.  —  I  have  learned  to  dread  a  slowly  developing 
ulcer,  in  chronic  X-ray  lesions,  which  may  or  may  not  be 
painful ;  the  edges  may  be  slightly  raised  and  a  little  indu- 
rated, or  soft  and  flat.  Nothing  but  the  persistence  of  the 
lesion  really  suggests  malignancy.  In  Case  XVII.,  though  an 
intermittent  ulceration,  never  completely  healed,  had  persisted 
for  seven  years,  only  beginning  carcinoma  was  shown  by  the 
microscope,  while  a  very  malignant  tumor,  either  cancer  or 


408  •  PORTER. 

sarcoma  on  the  forehead  progressed  very  rapidly  within  half 
a  year.  I  have  been  informed  that  ulcerations  have  been 
open  for  years  in  the  same  spot  in  two  cases,  and  then 
entirely  healed.  Such  variations  in  the  tendency  to  malig- 
nancy must  be  taken  into  consideration  in  advising  radical 
treatment.  On  the  other  hand,  pain  and  disability,  not  the 
fear  of  malignancy,  is  often  an  indication  for  operation. 
Even  rapid  histological  examination  may  be  unreliable,  for 
twice  I  have  found  undoubted  cancer,  after  amputation  on 
the  clinical  evidence,  when  a  small  piece  microscopically 
examined  was  negative. 

Treatment  of  ulcers,  benign  and  malignant.  —  If  an  ulcera- 
tion becomes  exquisitely  sensitive  and  painful,  raw  and  beefy 
red,  whether  or  not  the  base  is  indurated,  such  as  occurred  in 
1902  in  Case  XIX.,  and  recently  in  Case  XX.,  early  amputa- 
tion should  be  done.  As  a  rule  amputation  at  the  knuckle 
of  a  finger,  upon  which  a  carcinomatous  ulcer  has  developed, 
will  be  found  to  be  sound  and  conservative  treatment ;  but 
when  one  finds  that  multiple  lesions  upon  both  hands  have 
been  treated,  and  more  will  probably  occur  in  the  future,  in 
view  of  the  possible  reparative  power  of  the  skin,  and  the 
relatively  benign  character  of  these  epitheliomata,  if  treated 
early,  it  seems,  so  far  as  my  experience  goes,  that  conserva- 
tive treatment  (by  which  I  mean  local  excisions  or  minor 
amputation)  will  probably  be  adequate  to  control  metastases. 
Although  since  1902  Case  XIX,  has  developed  very  many 
carcinomata,  and  twice  at  least  operation  has  been  too  long 
delayed,  there  is  as  yet  no  evidence  of  increasing  glandular 
enlargement,  which  surely  would  have  occurred  long  ago, 
except  for  the  timely  operations.  It  is  not  unlikely  that  this 
relative  immunity  may  be  partially  explained  by  the  oblitera- 
tion of  the  adjacent  lymphatics,  which  has  been  induced  by  the 
X-rays.  It  must  become  a  question,  finally,  as  to  how  close  to 
the  wind  the  patient  and  surgeon  are  willing  to  sail.  For  ex- 
ample: this  same  Case  XIX.  developed  an  epithelioma  on  the 
stump  of  the  little  finger.  This  he  did  not  wish  to  sacrifice,  as 
the  forefinger  was  maimed,  so  after  thorough  excision, down  to 


SURGICAL   TREATMENT   OF   X-RAY    CARCINOMA.         4O9 

the  aponeurosis,  the  actual  cautery  was  thoroughly  applied. 
Healing  was  most  painful  and  slow,  yet  at  present,  six  months 
after  operation,  there  is  no  evidence  of  recurrence  and  the 
finger  is  soundly  healed.  One  case  has  remained  well  for 
two  years  and  a  half,  after  thorough  dissection  of  the  axilla 
for  cancerous  involvement;  one  of  my  patients  is  well  a  year 
and  a  half  after  a  similar  operation.  In  those  cases,  where 
there  have  been  many  epitheliomata  on  the  hands  and  fingers, 
it  must  be  a  serious  problem  as  to  whether  amputation  at  the 
wrist,  which  would  practically  guarantee  a  cure,  would  not  be 
sound  surgery;  yet  I  know  of  no  X-ray  operator  in  my 
experience  who  would  make  this  deliberate  choice. 

Skin  grafting.  —  I  have  been  so  successful  in  the  treat- 
ment of  these  cases  by  Thiersch  grafting  that  I  personally 
advise  it  in  all  of  the  more  severe  X-ray  lesions.  I  have  not 
used  Wolff"  grafts,  although  some  of  the  Thiersch  transplan- 
tations have  been  so  thick  as  to  practically  amount  to  the 
same  thing.  After  two  failures  in  using  skin  for  these 
grafts  from  parts  to  some  degree  affected,  I  am  convinced 
that  sound  skin  never  subjected  to  the  X-rays  has  more 
vitality.  Heterogeneous  grafts,  in  the  few  instances  in  which 
I  have  employed  them,  have  been  failures.  The  disinfec- 
tion of  these  cases  before  operation  is  a  difficult  problem, 
for  as  open  ulcerations  invite  sepsis  in  the  grafts  we  would 
prefer  thorough  germicidal  treatment;  but  this,  if  thoroughly 
carried  out,  usually  results  in  so  much  irritation  that  the 
subsequent  discharge  of  serum  is  excessive.  I  have  pre- 
ferred, therefore,  mechanical  rubbing  with  a  sponge  and 
salt  solution,  followed  by  carbolic  acid  solution  (1—50)  for 
a  few  moments.  If  the  skin  is  unbroken,  ordinary  methods 
are  applicable.  A  tourniquet  should  always  be  used,  for 
bleeding  is  free  and  dissections  must  be  delicate  when  made 
over  the  joints,  tendons,  or  aponeuroses.  After  the  removal 
of  the  diseased  tissues,  the  tourniquet  should  be  removed, 
and  the  hands  elevated  until  bleeding  has  stopped  spontane- 
ously. I  have  seen  little  benefit  from  peroxide,  and  have 
never  dared  to  use  adrenalin.     In  some  cases  the  hemostatic 


410  PORTER. 

action  of  grafts  quickly  placed  upon  an  oozing  surface  has 
been  remarkable.  If  possible,  excisions  should  have  bevelled 
edges,  and  the  graft  should  be  cut  thick  in  the  middle,  thin- 
ning out  towards  the  periphery,  so  that  it  will  accurately  fit 
the  wound.  Firm  pressure  must  be  applied  for  the  first 
twenty-four  hours  to  prevent  oozing  and  hemorrhage.  In 
order  to  insure  even  pressure  after  operation,  and  to  avoid 
danger  of  detachment  of  the  grafts  by  slight  motions  of  the 
etherized  patient,  the.  hand  and  fingers  must  be  firmly  fixed 
to  a  well-padded  splint  by  adhesive  plaster  before  any  of 
the  grafts  are  applied.  This  is  often  a  painstaking  proced- 
ure, owing  to  the  various  deformities  and  irregularities  in 
the  lengths  of  the  fingers  between  which  gauze  must  be 
placed  to  make  them  comfortable.  The  grafts  are  dressed 
with  small  pieces  of  protective  placed  in  an  imbricated  fash- 
ion, and  stuck  by  blood  to  the  palmar  surfaces  of  the  fingers  ; 
the  protective  should  be  perforated.  After  sufficient  gauze 
has  been  placed  over  the  protective  to  make  an  elastic 
dressing,  firm  pressure  should  be  made  directly  downwards 
by  series  of  opened  gauze  sponges  which  are  tied  on  the 
palmar  surface  of  the  splint.  By  this  manoeuvre,  detach- 
ment of  the  grafts  is  prevented,  as  I  have  frequently  seen 
when  a  roller  bandage  was  used,  causing  gradual  lateral 
creeping  of  the  grafts.  After  twenty-four  hours  the  pro- 
tective should  be  removed  with  great  care,  and  if  the  pain 
is  not  too  severe  the  grafts  should  be  exposed  to  the  air  in 
a  cage.  If  such  exposure  cannot  be  borne,  benzoinated  lard 
is  the  least  macerating  ointment  which  I  have  found.  Blisters 
are  punctured  as  fast  as  they  are  formed.  If  these  punctures 
scab,  and  serum  accumulates  under  the  graft,  dry  treatment 
is  contraindicated.  At  the  end  of  three  days  the  hands  are 
bathed  in  warm  salt  solution  or  citrate  of  silver;  while  under 
water  small  tabs  of  skin,  etc.,  may  be  very  readily  removed, 
as  in  making  a  wet  dissection.  In  ten  days  the  grafts  are 
soundly  healed,  when  dry  treatment  with  occasional  lanolin 
ointment  is  all  that  is  necessary.  The  patient  must  be  kept 
in  bed  for  four  or  five  days  with  the  hands  elevated.  If  the 
grafts  owing  to   infection   or  from   lack  of  blood   supply  do 


SURGICAL   TREATMENT   OF   X-RAY   CARCINOMA.         4 II 

not  take  over  the  aponeuroses,  a  subsequent  grafting  may  be 
done  when  the  wound  granulates,  provided  spontaneous  heal- 
ing does  not  take  place. 

SUMMARY. 

With  the  more  general  recognition  of  the  existence  of 
these  X-ray  carcinomata,  it  seems  clear  that  such  early  con- 
servative treatment  as  I  have  outlined  will  be  adequate  to 
prevent  metastases,  for  a  careful  study  of  the  fatal  cases 
shows  that  in  eight  of  them  inadequate  treatment,  either  in 
point  of  time  or  extent  of  operation,  due  almost  always  to 
refusal  of  the  patient  to  submit  to  the  treatment  suggested, 
was  the  cause  of  the  fatal  issue.  In  the  case  of  Sick,  and 
also  of  Wagner,  coincident  development  of  epithelioma  on 
the  face  or  other  parts  of  the  body  made  adequate  surgical 
treatment  more  difficult. 

[In  my  former  paper  I  was  indebted  to  Dr.  J.  H.  Wright,  Director  of 
the  Clinical  Laboratory,  and  to  Dr.  W.  F.  Whitney,  Pathologist  at  the 
Massachusetts  General  Hospital,  for  the  microscopical  reports  of  my 
cases.  Dr.  C.  J.  White,  Dermatologist  to  the  Hospital,  made  an  exhaus- 
tive study  and  report  of  the  numerous  sections  removed  from  Case  XIX., 
while  both  Dr.  Wright  and  Dr.  Whitney  have  examined  the  material  from 
many  of  my  subsequent  cases,  and  Professor  Mallory  of  the  Harvard 
Medical  School  has  given  me  his  valuable  opinion  on  two  cases.  Most 
of  the  pathological  specimens  have  been  sent  to  Dr.  S.  Burt  Wolbach  of 
the  Bender  Hygienic  Laboratory  in  Albany,  who  is  making  a  special 
study  of  X-ray  lesions  and  their  causative  relation  to  carcinoma.  As  his 
contribution  will  be  published  in  conjunction  with  this  paper,  I  devote 
myself  chiefly  to  the  clinical  side  of  the  subject,  leaving  to  him  a  more 
careful  description  of  the  pathological  lesions  found  in  the  less  advanced 
cases,  and  an  estimate  of  their  value  in  a  theoretical  attempt  to  explain 
the  etiology  of  cancer,  or  at  least  the  conditions  which  immediately  precede 
its  development.] 

REFERENCES. 

1.  E.  Schumann.  Beitrage  fiir  Klinische  Chirurgie,  1907,  Ixxxiv, 
Heft  3,  855. 

2.  Karl  Lindenborn.     Same  journal,  1908,  Ixxxix,  Heft  2,  385. 

3.  Dr.  Cecil  Rowntree.     Archives  of  the  Middlesex  Hospital,  xiii,july, 

lL,OS. 


412  PORTER. 

DESCRIPTION   OF   PLATES. 
Plate  XXXV. 

Fig.  I.  — Case  V.  Precancerous  ulceration.  Dr.  W.  H.  M.  Condition 
before  and  ten  days  after  operation. 

Fig.  2. — Case  VIII.  Miss  H.  Huge  X-ray  ulceration  with  epitheli- 
omatous  nodules,  as  marked  in  ink  square;  after  first  operation. 

Fig.  3. — Miss  H.  Condition  after  second  operation  with  outline  of 
extent  of  excision  with  subsequent  healing. 

Fig.  4.  —  Case  IX.     M,  K.  K.     1901 ;  note  pachydermia. 

Fig.  5.  — Same,  1903.  Note  ribbing  of  nails,  rhagades,  and  superficial 
ulcerations. 

Fig.  6. — Same,  January,  1908.  Carcinoma  base  of  ring  finger,  and 
over  terminal  phalanx  of  middle  finger  of  left  hand.  Keratosis  right 
hand. 

Plate  XXXVI. 

Fig.  7.  —  Case  XV.  F.  H.  S.  Epitheliomatous  ulcer  back  of  hand, 
with  numerous  keratoses  and  telangiectases. 

Fig.  8.  —  Same.     Low  power;  carcinoma  of  hand. 

Fig.  9.  —  Same.  Telangiectases  of  chest  with  carcinomatous  nodule 
outlined  in  ink  circle. 

Fig.  10.  —  Same.     Low  power;  nodule  chest;  epidermoid  carcinoma. 

Fig.  II.  —  Same.  Keratosis  nose,  high  power.  Note  extraordinary 
number  of  mitotic  cells. 

Fig.  12  —  X-ray  ulcer  leg.     Case  III. 

Plate  XXXVII. 

Fig.  13. — J-  G.  Case  XVIII.  Recurrent  growth  of  finger,  pushing 
through  skin  graft. 

Fig.  14. — Section  same  case,  low  power.  Note  encapsulated  growth 
and  small  carcinoma  on  right. 

Fig.  15.  —  High  power  of  same  growth.  Pathology  described  by  Pro- 
fessor Mallory,  under  Case  XVIII. 

Fig.  i6. — W.  J.  D.  Case  XIX.  Condition  of  hands,  June,  1905. 
Epithelioma  base  middle  finger,  right  hand. 

Fig.  17.  —  Same  case.  Condition  of  hands  July,  1907.  Epitheliomatous 
ulceration  forefinger.  Flexion  owing  to  destruction  of  extensor  tendon 
over  head  first  phalanx. 

Fig.  18.  —  Same  case.  Condition  November,  1908.  Epithelioma  base 
little  finger,  left  hand.    Malignant  keratosis  base  middle  finger,  right  hand. 

Plate  XXXVIII. 

Fig.  19. — W.J.  D.  Case  XIX.  March,  1909.  Present  condition 
after  thirty-four  operations. 


SURGICAL   TREATMENT   OF   X-RAY   CARCINOMA.         413 

Fig.  20.  —  X-ray  same  case,  March,  1909,  showing  no  osteoporosis,  in 
spite  of  long  duration  of  disease. 

Fig.  21. — Photomicrograph,  Case  XIX.,  showing  in  center,  nerve  sur- 
rounded by  carcinoma,  causing  intense  pain. 

Fig,  22.  —  H.  G.  Case  XVII.  Hand  one  year  after  operation.  Graft 
is  outlined;  note  thickness  of  skin,  keratoses  and  characteristic  nail 
changes. 

Fig.  23.  —  Case  XVII.  Recurrent  growth  on  forehead,  low  power. 
Question  of  sarcoma  or  carcinoma.     See  pathological  description. 


The  Journal  of  Medical  Research,  Vol.  XXI.,  No.  3,  October,  1909. 


,  Journal  of  Medical  Research. 


Vol.  XXI.    Plate  XXXV. 


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C.  A.  Porter. 


X  ray  lesions. 


Journal  of  Medical  Research. 


Vol.  XXI.    Plate  XXXVI. 


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11 


C.  A.  Porter. 


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X  ray  lesions. 


Journal  of  Medical  Research. 


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Journal  of  Medical  Research. 


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X  ray  lesions. 


THE   PATHOLOGICAL   HISTOLOGY    OF   CHRONIC    X-RAY   DER- 
MATITIS  AND    EARLY   X-RAY    CARCINOMA.* 

S.    B.    WOLBACH,    M.D. 

{^Director  of  the  Pathological  Laboratory,  Montreal  General  Hospital,  Montreal.^ 

The  development  of  multiple  carcinomata  in  the  skin  of 
patients  and  operators  who  have  suffered  repeated  injuries 
from  exposures  to  the  X-rays  has  occurred  so  many  times 
that  the  causal  relationship  has  been  generally  accepted  in  all 
countries.  The  tumors  have  made  their  appearance  in  each 
instance  reported,  several  years  after  the  establishment  of 
severe  chronic  changes  in  the  skin,  characterized  by  great 
thickening,  telangiectases,  ulceration,  hyperkeratosis,  and  loss 
of  the  epidermal  appendages. 

The  tumors  which    have    developed    in    the    permanently 
altered  skin  have  been  epidermoid  carcinomata  almost  invari-  . 
ably,    and     microscopically    cannot    be    distinguished    from 
similar  carcinomata  of  ordinary  occurrence. 

Striking  features  of  the  carcinomata  following  X-ray 
injuries,  already  brought  forth  in  numerous  publications, 
are  the  occurrence  in  young  individuals  and  the  malignant 
nature  of  the  tumors  as  shown  by  the  high  mortality.  The 
article  of  Dr.  C.  A.  Porter  in  this  issue  describes  the  clinical 
features  of  these  cases  and  presents  a  summary  of  those  from 
this  country. 

The  opportunity  to  make  a  careful  histological  study  of 
early  X-ray  carcinomata  and  of  skin  from  cases  showing 
varying  degrees  of  the  chronic  changes  which  precede  the 
occurrence  of  these  tumors  has  been  a  great  privilege  for 
which  I  am  indebted  to  Dr.  C.  A.  Porter.  His  interest  and 
care  has  also  made  it  possible  to  obtain  tissues  fixed  immedi- 
ately after  removal  from  the  patient.  In  every  instance  a 
general  anesthetic  was  employed  so  that  the  tissues  obtained 
were  not  injured  by  local  injections. 

All  of  the  material   studied   for  this  report   was   fixed    in 

*  Received  for  publication  July  26,  1909. 
(415) 


41 6  WOLBACH, 

Zenker's  fixative,  and  in  every  instance  immediately  after  oper- 
ation. The  staining  methods  employed  were  the  methylene 
blue  and  eosine  stain,  Mallory's  phosphotungstic  acid  hema- 
tein,  Mallory's  connective  tissue  stain  and  Verhoeff's  elastic 
tissue  stain  (all  are  described  in  the  Pathological  Technique 
of  Mallory  and  Wright,  fourth  edition). 

The  descriptions  were  made  chiefly  from  sections  stained 
by  the  phosphotungstic  acid  hematein  stain,  though  the 
other  stains  were  used  for  corroborative  evidence  when  neces- 
sary. This  stain  proved  to  be  especially  useful  in  the  study 
of  the  collagenous  fibrils  of  connective  tissue  because  it 
brings  out  differences  in  staining  properties  which  are 
not  demonstrable  by  the  other  methods  or  any  ordinary 
stain. 

As  the  use  of  Mallory's  phosphotungstic  acid  hematein 
stain  has  not  yet  become  general  a  brief  account  of  its  stain- 
ing qualities  is  desirable.  Nuclear  material  and  protoplasm 
are  stained  blue,  collagenous  fibrils  are  stained  brownish  red. 
Epidermal,  neuroglia,  myoglia,  and  fibroglia  fibrils  are 
stained  a  deep  blue.  Elastic  fibers  are  stained  either  a  deep 
purple  or  purple  with  a  brownish  periphery.  In  the  epider- 
mis the  superficial  layers  of  cells  stain  purplish  to  brownish 
red.     Most  cell  inclusions  stain  brownish. 

The  advantages  of  this  stain  in  a  histological  study  of  skin 
lesions  are : 

I.     Differential  staining  of  connective  tissue. 

II.      Differences  in   staining   of  normal   and   degenerated 
collagenous  material. 

III.  The  demonstration  of  fibrils  of  all  sorts  and  of  elastic 

fibers.  The  arrangement  and  development  of 
epidermal  fibrils  is  of  importance  in  the  study  of 
altered  function  of  epidermal  cells.  Myoglia  and 
fibroglia  fibrils  assist  in  the  identification  of 
smooth  muscle  and  connective  tissue  cells. 

IV.  The  ease  by  which  products  of  cell  degeneration  are 

recognized  when  within  the  cell. 


HISTOLOGY    OF   CHRONIC    X-RAY   DERMATITIS.         417 

V.  The  general  excellence  of  the  cell  pictures,  which  is 
largely  due  to  the  deep  staining  of  the  protoplasm, 
an  especially  valuable  feature  in  the  study  of  con- 
nective tissue  cells  in  dense  fibrous  tissue.  Eosin- 
ophilous  cells  may  be  recognized  by  the  presence 
of  deep  blue  stained  granules.  Mast  cells  are  not 
demonstrated,  owing  to  the  fixative  necessarily 
employed. 

The  effects  of  X-ray  exposures  upon  human  and  animal 
tissues  have  been  incompletely  determined.  Studies  from 
cases  similar  to  those  forming  the  basis  for  this  paper  have 
been  (ew  in  number,  and  although  the  most  important  of  the 
constant  changes  have  been  described,  no  single  observer 
has  had  the  opportunity  of  comparing  the  cases  from  a  series 
as  large  as  the  present  one.  Many  important  changes  have 
been  overlooked  owing  to  the  employment  of  inferior  staining 
methods. 

Case  I.  (Case  II.,  Dr.  Porter).  —  R.  M.,  a  man  aged'  55 
years  was  exposed  July  23,  1908,  for  not  more  than  twenty 
minutes  during  a  fluoroscopic  examination.  In  three  weeks 
a  painful  area  of  erythema  the  size  of  a  dinner  plate  appeared 
in  the  site  of  the  exposure.  The  edges  of  the  erythema  grad- 
ually subsided,  though  the  patient  continued  to  have  severe 
pain.  The  skin  broke  down  and  a  superficial  ulcer  3x2 
inches  resulted,  which  resisted  treatment  and  steadily 
increased  in  size.  On  Nov.  18,  1908,  the  whole  of  the 
ulcer  was  excised  with  a  wide  margin  of  surrounding  skin. 

The  material  received  for  examination  consisted  of  tissue 
hardened  in  Zenker's  fixative,  representing  a  large  ulcer 
about  ten  centimeters  in  diameter  surrounded  by  a  border  of 
epidermis  one  to  one  and  a  half  centimeters  in  width.  The 
tissue  includes  the  skin  and  subcutaneous  tissues  for  a  depth 
of  one-half  to  one  centimeter. 

■  Description,  under  the  microscope,  from  sections  stained 
with  phosphotungstic  acid  hematein.  The  most  striking 
lesions,  aside  from  the  ulceration,  are  found  in  the  connective 


41  8  wo  LB  AC  H. 

tissue  of  the  corium  and  subcutaneous  tissues.  The  corium 
everywhere,  beneath  the  ulceration  and  where  covered  with 
epidermis,  is  of  great  density.  Immediately  beneath  the 
epidermis,  however,  it  has  a  delicate  structure,  and  is  the  seat 
of  an  active  process.  The  subcutaneous  connective  tissue 
exhibits  marked  degenerative  changes,  including  deposits 
of  fibrin  and  reparative  processes  evidenced  by  the  presence 
of  young  connective  tissue  cells. 

The  deeper  layers  of  the  corium  are  composed  of  very 
dense  connective  tissue,  poor  in  cells,  with  thick  bundles  of 
deeply-staining  collagenous  fibrils.  The  latter  are  stained  a 
deep  red  and  form  bundles  many  times  thicker  than  occurs 
in  the  normal  corium.  The  fibrils  are  coarse  in  texture 
and  have  a  more  hyaline  refractive  appearance  than  those  in 
normal  skin.  In  places  there  are  bundles  in  which  the 
collagenous  fibrils  are  fused  into  homogeneous  refractive 
masses.  Elastic  fibers  are  very  numerous,  they  run  parallel 
to  the  collagenous  fibrils,  in  great  numbers  at  the  periphery 
of  bundles,  but  often  imbedded  within.  The  elastic  fibers 
vary  greatly  in  thickness,  many  can  be  easily  resolvd'd  only 
with  the  highest  oil  immersion  objective  (Zeiss  1.5  mm. 
apo.).  All  show  a  central  bluish  stained  core  with  a 
brownish  outer  zone.  The  connective  tissue  cells  show  no 
abnormalities. 

The  corium  immediately  beneath  the  epidermis  for  a  con- 
siderable depth  is  of  loose  texture,  contains  little  collagenous 
material  but  many  young  connective  tissue  cells.  The 
papillae  are  absent.  These  changes  are  most  marked,  near 
the  ulceration  and  gradually  diminish  in  the  direction  of  the 
periphery  of  the  excised  tissue.  Still  every  part  of  the 
material  examined  shows  absence  of  papillje  and  rarefication 
of  the  collagenous  material.  The  collagenous  fibrils  in  this 
part  of  the  corium  are  very  delicate  and  stain  less  deeply 
than  normal,  taking  a  pale  brownish  color.  The  individual 
fibrils  or  small  bundles  of  them  are  widely  separated.  The 
tissue  is  infiltrated  with  polymorphonuclear  leucocytes, 
lymphoid  and  plasma  cells  and  eosinophiles.  There  are 
numerous    large,    many    processed     connective    tissue     cells 


HISTOLOGY   OF   CHRONIC    X-RAY    DERMATITIS.         419 

having  extraordinarily  large  nuclei.  There  are  many  dilated 
capillaries  in  this  rarefied  corium,  made  conspicuous  by  the 
large  endothelial  cells  lining  them.  Migrating  endothelial 
cells  are  easily  found,  and  there  are  occasional  clusters  of 
them  surrounding  capillaries.  A  few  capillaries  are  filled 
with  free  endothelial  cells,  occasionally  one  contains  a  single 
giant  cell.  In  places  greatly  dilated  capillaries  lie  imme- 
diately beneath  the  epidermis.  The  epidermis  is  separated 
from  the  corium  by  a  basement  membrane,  usually  well 
defined,  but  in  places  composed  of  an  extremely  delicate 
hyaline  brownish  stained  material.  In  the  connective  tissue 
below  the  corium  are  large  areas  containing  deposits  of 
fibrin.  The  collagenous  fibrils  are  faintly  stained  and  in 
places  changed  into  a  hyaline  material.  Young  connective 
tissue  cells  are  numerous.  There  are  very  few  polymorpho- 
nuclear leucocytes,  lymphoid  and  plasma  cells  except  about 
the  remains  of  coil  glands.  The  fat  lobules  show  little 
change.  In  places  the  cell  walls  are  wrinkled  and  there  are 
accumulations  of  lymphoid  and  plasma  cells  between  the  fat 
cells  and  surrounding  capillaries. 

The  epidermis  is  uniformly  thickened.  The  horny  layer 
is  very  thin.  The  layers  of  prickle  cells  and  granular  cells 
are  of  increased  thickness.  In  a  few  places  the  epidermis  is 
separated  from  the  basement  membrane  by  spaces  filled 
with  finely  granular  material.  The  layer  of  basement  or 
cylindrical  cells  in  general  is  orderly  arranged,  but  in  places 
there  are  groups  of  deeply-stained  cells  which  are  irregularly 
arranged  upon  the  basement  membrane.  These  cells  are  of 
the  prickle  cell  type,  while  elsewhere  the  basement  cells  are 
of  the  normal  type.  In  these  atypical  groups  the  cells  are 
often  separated  by  narrow  clear  spaces.  The  prickle  fibrils, 
which  are  stained  a  deep  blue,  run  vertically  at  the  base  into 
the  basement  membrane  and  here,  in  places,  form  a  delicate 
blue  line  by  a  series  of  contiguous  arches. 

The  ulcerated  surface  is  covered  with  a  layer  of  coarse 
meshed  hyaline  fibrin.  In  most  places  the  fibrin  lies  directly 
upon  degenerated  collagenous  material,  but  there  are  some 
large  areas  of  granulation  tissue. 


420  WOLBACH. 

The  smooth  muscle  in  all  sections  examined  shows  very 
marked  changes  in  the  walls  of  vessels  and  in  the  arrector 
pili  muscles.  In  the  latter  the  cells  are  of  increased  thick- 
ness, and  the  myoglia  fibrils  are  of  unusual  size,  though  this 
may  be  due  to  the  fusion  of  fibrils.  Many  of  the  cells  are 
vacuolated,  others  are  filled  with  a  hyaline  brownish  stained 
material.  In  arteries  and  veins  of  the  subcutaneous  tissues 
the  muscle  cells  show  the  same  changes  as  in  the  arrector 
pili  muscles,  though  there  are  many  atrophic  muscle  cells 
which  are  surrounded  by  dense  collagenous  material  of 
which  there  is  a  great  increase  in  the  media.  In  some  ves- 
sels most  of  the  muscle  fibers  in  a  given  section  are  swollen, 
widely  separated  by  connective  tissue  and  all  are  filled  with 
masses  of  h\-aline  brownish  stained  material. 

Besides  the  thickening  of  the  media  above  noted,  a  few 
arteries  and  veins  show  marked  thickening  of  the  intima  due 
to  an  increase  of  connective  tissue  and  to  swelling  and 
vacuolization  of  the  endothelium.  Many  arteries  and  veins 
are  normal  in  appearance.  In  the  arteries  showing  the 
above  changes  the  elastic  lamina  has  disappeared  and  its 
place  is  occupied  by  a  thick  dense  band  of  hyaline  fibrillary 
material  stained  brownish  and  probably  collagenous  in  nature. 

Hair  bulbs  and  sebaceous  glands  are  absent  in  all  parts  of 
this  specimen.  Certain  linear  areas  filled  with  inflammatory 
cells  and  young  connective  tissue  cells  undoubtedly  represent 
the  sites  once  occupied  by  these  structures. 

Remains  of  coil  glands  are  found  in  all  sections.  The 
changes  are  those  of  simple  atrophy  —  degeneration  with 
infiltration. 

Case  II.  (Case  III.,  Dr.  Porter).  —  E.  R. ;  female;  30 
years.  Was  treated  with  the  Rdntgen  rays  for  ulcerations  on 
outer  side  of  knee  and  elbow  for  about  one  month  during 
March  and  April  of  1908.  Healing  of  the  ulcers  followed, 
then  rapid  breaking  down,  ulceration,  and  severe  acute 
dermatitis.  From  Aug.  18  until  Nov.  7,  1908,  there  was 
severe  pain  from  the  dermatitis  and  ulcerations.  Examina- 
tion   Dec.    4,    1908,    showed    characteristic    X-ray    changes 


HISTOLOGY    OF   CHRONIC   X-RAY   DERMATITIS.  42 1 

over  the  inner  aspect  of  the  right  elbow.  The  skin  was 
thickened,  there  were  telangiectases  and  a  small  ulcera- 
tion covered  with  a  yellow  fibrinous  layer.  There  was 
marked  dermatitis  of  the  left  leg  from  the  middle  of  the 
thigh  to  the  top  of  the  boot.  On  the  outer  side  of  the  knee 
there  was  an  area  six  by  five  inches  showing  reddened  pig- 
mented scars  which  have  healed  peripherally,  leaving  in 
the  center  an  ulceration  three  by  one  inches  in  extent. 
Jan.  21,  1901,  the  ulcer  was  removed  with  a  surrounding 
zone  of  skin  one-half  inch  in  diameter. 

This  tissue  was  received  after  hardening  in  Zenker's  fixa- 
tive. It  consisted  of  an  ulcer  of  the  skin  three  and  a  half  by 
one  and  two-tenths  centimeters  in  extent  surrounded  by  a 
zone  of  epidermis  one  to  one  and  a  half  centimeters  in 
width.  The  disc  of  tissue  was  about  one  centimeter  thick 
and  included  the  subcutaneous  fat. 

Description  under  the  microscope.  There  are  the  same 
changes  in  this  specimen  that  were  found  in  Case  I.  There 
are  differences  of  degree,  however,  that  deserve  description. 

The  deeper  layers  of  the  corium  contain  dense  collagenous 
material  similar  to  that  in  Case  L  There  are,  however, 
more  numerous  and  larger  connective  tissue  cells  throughout. 
Towards  the  zone  of  rarefied  corium  there  is  a  very  cellular 
layer  of  connective  tissue,  the  cells  of  which  occur  singly  or 
in  groups  and  are  separated  by  wide  bands  of  refractive 
hyaline  collagenous  material.  The  connective  tissue  cells 
are  large  with  prominent  nuclei  and  abundant  protoplasm 
having  many  processes  and  conspicuous  fibroglia  fibrils. 
Elastic  fibers  are  present  in  extraordinary  numbers,  in 
places  they  run  in  directions  parallel  to  the  connective  tissue 
cells  and  many  are  in  contact  with  connective  tissue  cells. 

The  connective  tissue  between  the  lobules  of  the  subcu- 
taneous fat  is  dense  and  similar  to  that  of  the  corium. 

The  vessels  show  much  more  marked  changes  than  in  Case 
I.  There  are  numerous  completely  obliterated  arteries  and  all 
of  the  vessels  in  the  sections  show  thickening  of  the  walls 
with  reduction  of  the  caliber  of  the  lumen.     The  obliteration 


422  WOLBACH. 

and  thickening  of  the  walls  is  due  to  proliferation  of  con- 
nective tissue  in  the  intima  and  media  and  to  increased  thick- 
ness of  the  smooth  muscle  fibers.  In  vessels  showing  lesser 
changes,  the  muscle  fibers  of  the  media  are  large,  and  widely 
separated  by  coarse  collagenous  fibrils  and  vacuoles.  The 
location  of  the  vacuoles  is  difficult  to  determine.  Some  of 
them  are  within  young  connective  tissue  cells,  which  are 
increased  in  number  particularly  in  the  adventitia.  The 
smooth  muscle  fibers  are  swollen,  many  contain  two  to  four 
nuclei.  The  rnyoglia  fibrils  are  either  normal  in  appearance 
or  more  conspicuous  than  the  normal.  Where  the  process 
is  more  advanced,  the  smooth  muscle  fibers  are  surrounded 
by  dense  fibrous  tissue,  the  'myoglia  fibrils  cannot  be  dem- 
onstrated and  the  protoplasm  has  become  homogeneous  and 
hyaline  in  appearance  and  takes  a  brownish  blue  stain. 

The  thickening  of  the  intima  is  due  to  the  presence  of  a 
dense  yet  cellular  fibrous  tissue.  In  the  arteries  the  elastic 
lamina  is  usually  totally  absent,  its  place  being  indicated  by 
a  dense  band  of  collagenous  material.  Occasionally  remains 
of  the  elastic  lamina  are  found  and  in  these  the  elastic  tissue 
is  broken  up  into  delicate  filaments  which  stain  a  deep 
brownish. 

The  endothelium  is  often  redundant,  the  cells  are  large, 
cuboidal  or  elongated  in  shape  and  often  contain  large 
vacuoles.  The  above  changes  are  most  marked  in  the  arter- 
ies. In  the  veins  the  media  shows  less  marked  changes  and 
the  thickening  of  the  walls  and  diminution  of  caliber  of  the 
lumen  is  due  chiefly  to  a  thick  concentric  layer  of  large  con- 
nective tissue  cells,  with  much  or  little  collagenous  inter- 
cellular substance  in  the  intima. 

The  corium  just  below  the  epidermis  shows  more  marked 
rarefication  and  contains  more  and  larger  telangiectases  than 
that  in  Case  I.  Many  very  large  blood  spaces  lie  directly  in 
contact  with  the  epidermis,  separated  only  by  a  narrow  border 
of  hyaline-changed  collagenous  material.  Others  are  sur- 
rounded by  necrotic  tissue  and  are  filled  with  fibrin. 

The  many  capillaries  just  beneath  the  epidermis  are  lined 
with     large    endothelial    cells,    a    few    are    filled    with    loose 


HISTOLOGY    OF   CHRONIC   X-RAY   DERMATITIS.  423 

endothelial  cells.  In  occasional  areas  capillaries  thus  occluded 
are  found,  about  which  all  of  the  connective  tissue  has  under- 
gone hyaline  change. 

The  epidermis  is  uniformly  markedly  thickened.  In  gen- 
eral the  relations  of  the  different  cell  strata  are  the  same  as 
in  Case  I.  But  there  are  many  places  in  the  tissue  where 
the  lowermost  layers  of  cells  present  differentiated  groups 
and  strata  of  large  deeply-stained  cells.  In  places  where  the 
basement  membrane  is  not  demonstrable  there  are  irregularities 
of  the  bottom  layer  of  cells  and  individual  cells  are  some- 
times found  in  spaces  of  the  corium,  though  always  connected 
above  with  the  epidermis.  Irregular  downgrowths  between 
adjacent  telangiectases  are  common,  though  there  is  nowhere 
any  evidence  of  actual  invasion  or  of  independent  growth, 
except  the  doubtful  evidence  of  increased  size  of  the  cells  and 
a  marked  affinity  for  basic  stains.     IMitoses  are  very  rare. 

Hair  bulbs  and  sebaceous  glands  are  entirely  absent. 
Areas  of  intense  infiltration  and  active  connective  tissue  mul- 
tiplication probably  represent  the  former  site  of  these  struc- 
tures. A  few  atrophic  remains  of  coil  glands  are  found 
surrounded  always  by  lymphoid  and  plasma  cells. 

The  ulcerated  surface  of  the  tissue  is  covered  for  the  most 
part  with  granulation  tissue.  In  many  places  dense  hyaline 
fibrous  tissue,  infiltrated  with  polymorphonuclear  leucocytes, 
is  directly  exposed.  There  is  in  places  slight  downgrowth  of 
the  epidermis  at  the  edges  of  the  ulcer  comparable  to  that 
found  in  cases  of  chronic  ulcer. 

Case  III.  (Case  IV.,  Dr.  Porter).  — F.  H.  S. ;  male;  40 
years.  Received  Rontgen  ray  treatment  for  eczema  five 
years  ago.  There  was  marked  improvement  of  the  eczema 
and  during  that  year  occasional  treatments  were  given  which 
finally  resulted  in  a  severe  dermatitis  with  exfoliation  of  the 
skin  of  both  thighs  and  legs.  Four  years  ago  a  small  ulcer 
developed  on  the  inner  side  of  the  calf  and  has  never  healed. 
Another  small  ulcer  which  formed  on  the  thigh  healed  after 
a  few  months.  There  has  been  no  pain.  In  August,  1908, 
the  ulceration  of  the  left  leg  began  to  spread  rapidly,  in  spite 


424  WOLBACH. 

of  various  forms  of  treatment  including  two  applications  of 
radium.  Examination  on  Nov.  lo,  1908,  showed  an  irregu- 
larly-shaped ulcer  three  by  two  and  a  fourth  inches.  In  the 
center  there  were  occasional  islands  of  growing  epidermis, 
the  rest  was  covered  with  fibrinous  exudate.  The  skin  was 
undermined  and  showed  no  evidence  of  repair.  The  whole  was 
excised  on  Nov.  19,  1908.  The  tissue  received  for  examina- 
tion had  been  hardened  in  Zenker's  fixative.  It  included  the 
ulcer  and  subcutaneous  fat  with  a  surrounding  margin  of 
skin  one  centimeter  in  width. 

Examination  under  the  microscope.  —  The  deeper  layers  of 
the  corium  are  composed  of  the  same  dense  tissue  found  in 
Cases  I.  and  11.  In  places  there  are  very  many  young  con- 
nective tissue  cells  with  conspicuous  fibroglia  fibrils  in  the 
meshes  of  hyaline-changed  collagenous  fibers.  Some  of 
these  connective  tissue  cells  are  surrounded  by  narrow  zones 
of  paler  staining  normal  collagenous  fibrils.  The  picture 
suggests  the  proliferation  of  connective  tissue  and  the  deposit 
of  fresh  collagenous  material  in  the  meshes  of  degenerated 
fibrous  tissue. 

The  corium  immediately  beneath  the  epidermis  shows  the 
changes  previously  described,  i.e.,  the  more  delicate  structure, 
presence  of  young  connective  tissue  cells,  dilated  blood 
spaces,  absence  of  papillae  and  occasional  thrombosed  tel- 
angiectases in  contact  with  the  epidermis. 

The  ulcerated  surfaces  show  active  granulation  tissue  enclos- 
ing masses  of  hyaline  changed  collagenous  material.  The 
granulation  tissue  arises  from  a  base  of  very  cellular  connec- 
tive tissue  in  which  the  connective  tissue  cells  are  imbedded 
in  degenerated  collagenous  material.  The  epidermis  is 
markedly  thickened.  The  horny  layer  is  almost  lacking. 
The  granular  layer  is  narrow,  so  that  the  width  of  the  epider- 
mis is  composed  chiefly  of  prickle  cells.  At  the  edges  of 
the  ulcer  are  downgrowths  of  the  epidermis  into  the  granu- 
lation tissue. 

The  blood  vessels  show  very  marked  changes.  Many 
large   arteries   of   the   corium   and    subcutaneous    tissue    are 


HISTOLOGY    OF    CHRONIC    X-RAY    DERMATITIS.  425 

completely  obliterated.  In  these  sections  it  can  be  shown 
that  the  characteristic  irregularity  of  the  muscle  fibers  is 
largely  due  to  the  ingrowth  from  the  adventitia  of  large 
fibroblasts,  the  prominent  fibrils  of  which  make  it  difficult  to 
distinguish  these  cells  from  smooth  muscle  cells.  The  first 
suspicion  that  some  of  the  cells  of  the  media,  while  appar- 
ently smooth  muscle,  were  connective  cells  was  awakened  by 
the  finding  of  branched  cells  with  coarse  fibrils.  Some  of 
these  cells  are  surrounded  by  considerable  collagenous 
material  and  these  facts  together  with  the  presence  of  occa- 
sional mitoses  prove  the  connective  tissue  origin  of  these  cells. 
The  vacuoles  in  the  media  are  probably  within  degenerated 
smooth  muscle  cells.  Some  small  veins  and  arteries  have 
the  media  completely  replaced  by  dense  collagenous  material 
in  which  atrophic  remains  of  smooth  muscle  cells  can  be 
found.  In  all  partially  or  completely  obliterated  arteries  the 
elastic  lamina  is  replaced  by  a  thick  convoluted  band  of 
dense  collagenous  material.  In  a  few  large  vessels  the 
endothelium  of  the  intima  is  strikingly  swollen  and  redundant 
and  many  of  the  cells  contain  large  clear  vacuoles. 

The  appendages  of  the  skin  are  absent.  Remains  of  the 
arrector  pili  muscles  are  found  consisting  of  tracts  of  young 
connective  tissue  enclosing  degenerated  smooth  muscle  cells. 

Case  IV.  (Case  VIII.,  Dr.  Porter).  —  Female;  40  years; 
S.  After  an  abdominal  hysterectomy  for  a  tumor  of  the 
uterus  was  treated  with  the  Rontgen  rays  for  a  slowly  grow- 
ing tumor  of  the  abdominal  wall  which  appeared  one  year 
after  operation.  She  received  one  hundred  and  thirty-six 
treatments  between  Jan.  28,  1902,  and  May  20,  1904. 
She  was  well  for  four  years,  when  characteristic  Rontgen 
ray  ulcerations  developed,  involving  the  whole  lower  abdo- 
men. There  was  necrosis  and  ulceration  of  the  skin  with 
nodules  suggesting  small  carcinomata.  On  March  7,  1908, 
the  whole  area  of  skin  containing  ulcers  was  excised  down  to 
the  aponeurosis  of  the  abdominal  muscles,  where  a  mass  of 
dense  tissue  was  encountered,  supposedly  the  remains  of  the 
tumor  for  which  treatment  was  given. 


426  WOLBACH. 

Description  of  gross  appearances  of  excised  tissue  (by  Dr.  Thomas 
Ordway).  "The  specimen  consists  of  a  large  irregularly  triangular 
piece  of  skin  and  subcutaneous  tissue.  Its  base  is  9  centimeters  and  the 
sides  are  10  centimeters  and  11. 5  centimeters  respectively.  It  is  from 
2  to  2.5  centimeters  thick  except  in  the  central  part,  where  it  is  .5  centi- 
meter to  .7  centimeter  thick.  The  skin  surface  shows  a  large  irregularly 
triangular  ulcer  (5.2  centimeters  x  7.5  centimeters  x  8  centimeters)  con- 
forming in  general  to  the  shape  of  the  specimen.  The  base  of  the  ulcer 
is  depressed  from  .2  centimeter  to  .6  centimeter  below  the  rough,  irreg- 
ular, ragged,  overhanging  and  undermined,  non-indurated  edges.  The 
edges  are  necrotic,  reddish-gray  in  color,  and  bathed  in  bright  yellow  puru- 
lent exudation.  The  base  of  the  ulcer  is  bright  red  to  grayish  red  in  color ; 
it  is  rough  and  ragged  and  is  irregularly  covered  with  purulent  exudate. 

"  The  lower  surface  of  the  specimen  consists  of  bright  yellow  fat  tissue 
through  which  is  a  delicate  tracery  of  grayish  white  fibrous  tissue.  In  the 
central  part  of  this  surface  of  the  specimen  (the  thinner  area  referred  to 
above)  there  is  an  area  (3.5  centimeters  x  4  centimeters)  of  firm,  dense, 
grayish  white,  glistening,  elastic  fibrous  tissue  which  is  found  to  be,  in 
many  places,  in  continuity  with  the  base  of  the  ulcer,  in  other  places  it  is 
connected  by  fine  and  coarse  fibrous  strands. 

"The  margin  of  the  skin  surrounding  the  ulcer  is  from  i  to  3  centi- 
meters in  width.  It  is  thicker  and  firmer  than  normal  skin  ;  it  is  diffusely 
reddened  with  a  deep  punctate  erythema  except  for  numerous  slightly 
elevated,  rounded,  whitened  areas  (.3  centimeter  to  .6  centimeter  in  size) 
which  have  a  distinct  nodular,  almost  '  shotty,'  feel.  On  section  these 
nodules  are  .4  centimeter  to  .6  centimeter  in  thickness.  The  surrounding 
skin  is  .2  centimeter  to  .3  centimeter  thick.  The  bright  punctate  appear- 
ance in  the  diflfuse  erythema  of  the  skin  surrounding  the  ulcer  is  appar- 
ently due  to  marked  injection  of  very  small  blood  vessels." 

Microscopic  examination  :  I.  Disc  of  fibrous  tissue  below 
floor  of  ulcer.  The  tissue  consists  chiefly  of  dense  fibrous 
tissue,  the  bundles  of  which  run  in  all  directions.  There  are 
groups  of  bundles  where  the  collagenous  fibrils  are  fused  into 
hyaline  masses  and  regions  where  the  connective  tissue  is  very 
cellular  and  edematous  in  appearance.  The  latter  areas 
surround  thin  walled  vessels  which  often  are  immediately 
surrounded  by  fibrin.  Many  arteries  and  capillaries  are  sur- 
rounded by  masses  of  lymphoid  and  plasma  cells  with  occa- 
sional eosinophiles.  The  amount  of  elastic  tissue  is  small, 
and  that  present  is  in  small  masses  composed  of  swollen  tor- 
tuous poorly-staining  clumps. 

II.      Sections  of  skin  surroundini^  the  ulcer.      The  corium 


HISTOLOGY   OF   CHRONIC   X-RAY   DERMATITIS.         427 

is  composed  of  dense  fibrous  tissue  rich  in  elastic  fibers  and  is 
in  general  similar  to  the  tissues  already  described.  There  is, 
however,  no  hyaline  change  of  the  collagenous  material,  and 
there  are  no  areas  containing  many  young  connective  tissue 
cells.  The  corium  immediately  beneath  the  epidermis  shows 
remains  of  the  papillary  structure,  but  shows  the  same  rarefi- 
cation  and  other  characteristics  noted  in  the  other  cases. 
There  are  numerous  large  connective  tissue  cells  in  this  part 
of  the  corium  with  abundant  spongy  protoplasm  and  numerous 
coarse  fibrils  (Foam  cells  of  Unna).  Particularly  striking  is 
the  occurrence  of  a  layer  of  homogeneous  hyaline  changed 
collagenous  material  separating  the  epidermis  from  the  cellu- 
lar loose  connective  tissue  below.  In  places  this  hyaline 
layer  contains  migrating  polymorphonuclear  leucocytes,  and 
occasionally  there  are  groups  of  a  few  small,  widely  separated 
epidermal  cells  occupying  spaces  in  this  layer,  surrounded 
and  infiltrated  with  leucocytes. 

The  epidermis  is  much  increased  in  thickness,  chiefly  due 
to  the  great  depth  of  the  prickle  cells.  Mitotic  figures  are 
common  in  the  basement  row  of  cells.  Some  of  the  large 
subcutaneous  arteries  show  eccentric  thickenings  of  the  walls. 

None  of  the  sections   show  any  trace  of  hair  follicles  or 
glands.     An  occasional  remains  of  the  arrector  pili  muscles . 
is  found  in  wnich  the  muscle  fibers  are  small,  vacuolated  and 
hyaline  degenerated.     The  fibrils  are  usually  demonstrable. 

III.  Sections  of  the  elevated  areas  of  skin  or  nodules 
found  in  the  skin  surrounding  the  ulcer.  The  elevation  of 
these  areas  is  due  to  a  great  increase  in  dense  fibrous  tissue 
in  the  corium,  which  extends  down  as  a  continuous  layer  to 
the  subcutaneous  fat.  Laterally  it  gradually  merges  into  the 
corium  of  the  surrounding  skin;  there  is  no  line  of  demarca- 
tion. The  bundles  of  collagenous  fibers  in  the  nodules  and 
surrounding  skin  are  very  dense  and  hyaline  in  appearance. 
The  number  of  elastic  fibers  is  enormously  increased.  There 
are  no  papillae  so  that  the  epidermis  lies  evenly  upon  dense 
hyaline  collagenous  material  or  in  places  upon  rarefied  con- 
nective tissue;  in  the  latter  case  there  is  a  line  of  hyaline 
collagenous  material  without  nuclei  immediately  beneath  the 


42  8  wo  LB  AC  H. 

epidermis.  There  are  numerous  telangiectases  beneath  the 
epidermis  and  in  the  dense  corium  are  large  blood  spaces 
lined  only  with  endothelium.  The  skin  surrounding  the 
nodules  shows  marked  rarefication  of  the  upper  layer  of  the 
corium  which  contains  many  large  telangiectases,  some  of 
them  filled  with  fibrin  ;  most  of  them  are  surrounded  by  zones 
of  hyaline  collagenous  material  continuous  with  the  layer 
beneath  the  epidermis. 

The  epidermis  in  places  is  greatly  thickened  and  there  are 
processes  extending  down  between  the  dilated  blood  spaces 
or  telangiectases.  Some  of  these  processes  are  thick  and 
branched  and  contain  typical  epithelial  pearls  (Figs.  13  and 
14).  They  are  always  surrounded  by  zones  of  lymphoid 
and  plasma  cells  and  an  occasional  eosinophilic  cell.  There 
are  numerous  mitoses  present  in  these  processes  and  in  the 
adjacent  epidermis. 

IV.  The  ulcer  and  adjacent  skin.  The  floor  of  the 
ulcer  consists  of  granulation  tissue  covered  with  fibrin  and 
purulent  exudate.  In  numerous  places  the  ulceration  extends 
nearly  to  the  subcutaneous  fat.  The  granulation  tissue 
includes  islands  of  degenerated  collagenous  material.  In 
places  there  is  no  granulation  tissue  and  degenerated  colla- 
genous material,  infiltrated  with  leucocytes,  forms  the  floor 
of  the  ulcer. 

The  corium  adjacent  to  the  ulcer  shows  the  changes  de- 
scribed in  the  sections  from  the  other  parts  of  this  tissue  ; 
hyaline  change  of  the  collagenous  fibrils,  and  a  diff"use 
appearance  of  new  connective  cells  between  the  collagenous 
bundles  without  the  formation  of  granulation  tissue.  Beneath 
the  epidermis  there  are  the  same  changes  observed  in  the 
other  sections.  Near  the  edge  of  the  ulcers,  however,  there 
are  many  large  telangiectases  some  of  which  are  filled  with 
fibrin  (Figs.  4  and  5).  In  places  the  fibrin  extends  through 
the  walls  of  the  vessel  into  the  surrounding  tissue.  In  a  few 
places  where  a  dilated  thrombosed  vessel  is  surrounded  by 
epidermis  there  are  masses  of  epidermal  cells  extending  into 
the  fibrin  (Figs.  8  and  9).  These  cells  form  tortuous  cords 
and   irregular  masses  of   cells  sometimes   nearly  completely 


HISTOLOGY   OF   CHRONIC    X-RAY   DERMATITIS.         429 

filling  the  vessel.  In  other  places  compact  groups  of  cells 
from  the  epidermis  extend  for  considerable  distances  into  the 
corium,  and  the  relations  of  these  epidermal  processes  is  such 
as  to  make  it  certain  that  extension  has  taken  place  into 
and  along  the  course  of  one  of  the  dilated  vessels.  These 
cell  processes  show  epithelial  pearls  and  many  mitoses. 
Occasionally,  in  such  a  process  a  group  of  epithelial  cells  is 
found  which  stains  more  deeply  than  the  surrounding  cells, 
and  the  individual  cells  show  great  irregularity  in  shape  with 
distorted  fibrils,  many  of  which  are  intracellular  (Fig.  14). 
Here  and  there  in  the  basal  layer  are  groups  of  epidermal 
cells  which  contain  large  irregular  nuclei  often  with  budding 
processes  containing  chromatin  material.  There  are  also 
cells  containing  two  or  more  nuclei.  The  cells  of  these 
groups  are  closely  packed  and  are,  roughly,  concentrically 
arranged,  individually  the  cells  are  approximately  spindle 
shaped.  Numerous  mitoses  are  also  found  in  these  small 
groups  of  cells  and  the  whole  picture  suggests  that  these 
groupsrepresent  isolated,  independently-growing  portions  of 
the  epidermis. 

Many  large  arteries  and  veins  of  the  subcutaneous  tissue  and 
corium  are  completely  obliterated  chiefly  through  the  multi- 
plication of  connective  tissue  cells  of  the  intima  (Figs.  18, 
21,  and  22).  In  some  instances  the  muscle  cells  of  the  media 
are  largely  replaced  by  leucocytes  and  fibroblasts  (Fig.  22). 
In  general  the  obliterated  vessels  show  the  same  characteris- 
tics as  those  described  in  preceding  cases. 

Case  V.  (Case  XV.,  Dr.  Porter).  —  Male;  40  years;  a 
maker  of  Rontgen  ray  tubes  since  1897.  ^^^  had  several 
acute  attacks  of  "  eczema."  The  first  ulceration  commenced 
in  1905  on  the  left  hand  between  the  knuckles  of  the  first  and 
second  fingers.  This  has  healed  and  broken  down  several 
times.  At  the  time  of  operation,  in  April,  1908,  there  were 
several  keratoses  and  small  ulcerations  on  the  hands.  On  the 
whole  there  has  been  very  little  pain  associated  with  any  of 
the  lesions.  The  tissues  excised  were  an  ulcer  from  the  back 
of  the  left  hand,  measuring  about  two   by  one  centimeters ; 


430  WOLBACH. 

a  horny  keratosis  from  between  the  knuckles  of  the  index 
and  middle  fingers  of  the  left  hand,  a  soft  wart-like  growth 
from  the  nose  one-half  centimeter  in  diameter  capped  with  a 
layer  of  horny  epithelium  and  a  piece  of  tissue  from  the 
chest  which  came  from  the  center  of  a  thickened  pigmented 
area  of  the  skin  showing  prominent  telangiectases  (the  chest 
has  been  frequently  exposed  to  the  rays  in  making  fluoro- 
scopic examinations).  This  piece  of  tissue  from  the  chest  had 
a  scaly  surface  with  minute  elevated  scar-like  areas.  The 
excision  included  all  the  tissues  of  the  skin  and  subcutaneous 
fat. 

Microscopic  examination :  I.  Keratosis  from  the  back 
of  the  hand  (Fig.  i6).  The  greatly  thickened  epidermis  has 
long  processes  extending  into  the  corium.  Between  the 
processes  of  epidermis  are  papillae  of  the  corium,  usually 
long  and  slender,  but  occasionally  short  and  thick  and  con- 
taining dilated  blood  spaces  filled  with  fibrin  and  leucocytes. 
The  collagenous  material  of  the  papillae,  as  elsewhere  in  the 
corium  immediately  beneath  the  epidermis,  shows  the  hya- 
line change  and  rarefication  noted  in  the  other  cases.  The 
vessels  in  the  papillae  are  of  large  caliber  and  many  are  sur- 
rounded by  areas  of  faintly  stained  collagenous  material  in 
which  are  strands  of  fibrin  and  young  connective  tissue  cells. 
Collections  of  plasma  cells  are  common  in  the  neighborhood 
of  capillaries  and  at  the  tips  of  the  epithelial  processes.  The 
cell  masses  also  contain  numerous  mononuclear  eosinophiles 
and  lymphoid  cells  and  occasionally  polymorphonuclear 
leucocytes.  The  deeper  part  of  the  corium  is  of  the  dense 
hyaline  type,  with  great  numbers  of  elastic  fibers,  already 
described. 

None  of  the  sections  include  the  large  vessels  of  the  deep 
corium  and  subcutaneous  tissues. 

The  epithelial  processes  of  the  epidermis  consist  of  prickle 
cells  with  an  abrupt  change  towards  the  surface  into  cells  of 
the  type  of  the  stratum  lucidum  (Fig.  19).  Cells  of  the 
granular  layer  type  are  almost  entirely  absent.  The  horny 
layer  is  very  thick  and  consists  of  fused   elements  in   which 


HISTOLOGY    OF   CHRONIC    X-RAY    DERMATITIS.         43 1 

cell  and  nuclear  outlines  can  often  be  distinguished  (acantho- 
sis). In  places  there  are  spaces  in  the  horny  layer  contain- 
ing refractive  hyaline  transformed  cells  in  which  are  nuclear 
remains.  The  basement  layer  of  cells  of  the  epithelial  pro- 
cess is  for  the  greater  part  regularly  arranged  and  composed 
of  columnar  cells.  In  places  the  arrangement  is  irregular, 
the  cells  are  irregular  in  shape  and  widely  separated.  Such 
groups  are  invaded  by  plasma  cells  and  polymorphonuclear 
eosinophiles.  The  epithelial  cells  show  numerous  mitoses 
and  in  general  are  small  in  size  and  show  very  prominent 
prickle  fibrils.  In  places  there  is  growth  of  epidermis  into 
dilated  vessels  filled  with  fibrin  which  lie  in  the  papillae  or  at 
the  base  of  the  keratosis.  The  epidermis  on  each  side  of 
the  keratosis  is  uniformly  thickened  and  for  the  most  part 
lies  upon  a  rarefied  corium  without  papillae.  In  places  there 
are  processes  of  epidermis  extending  into  the  corium,  usually 
around  or  between  telangiectases.  The  cells  of  such  pro- 
cesses consistof  irregularly  shaped  many  processed  pricklecells 
with  no  definite  arrangement.  Mitoses  are  common.  These 
groups  of  cells  are  invaded  with  plasma  cells  and  eosinophile 
cells  and  in  general  present  an  at\'pical  arrangement  and 
relationship  to  the  surrounding  densely  infiltrated  corium.  In 
addition  to  such  processes  there  are  long  stretches  of  epider- 
mis where  the  deeper  layers  consistof  similar  cells  with  simi- 
lar atypical  arrangement. 

Keratosis  from  tip  of  nose  (Fig  17).  The  gross  structure 
is  similar  to  the  lesion  from  the  hand.  The  changes  in  the 
corium  are  also  similar.  The  epidermis  is  strikingly  differ- 
ent because  the  entire  depth  of  the  epithelial  processes  are 
composed  of  a  uniform  type  of  cell ;  large  cells  with  great 
numbers  of  mitoses.  There  are  three  or  four  mitoses 
to  every  oil  immersion  field  even  immediately  beneath  the 
layer  of  horny  cells,  in  some  fields  there  are  eight  to  ten 
mitoses  (Fig.  23).  Prickle  fibrils  can  occasionally  be  dem- 
onstrated ;  usually  they  are  absent.  There  is  a  thin  la}'er  of 
horny  epithelium  which  is  in  many  places  detached  from  the 
active  cells  below. 


432  WOLBACH. 

At  the  base  of  the  epithelial  processes  there  are  irregular 
offshoots  extending  into  the  corium,  always  surrounded  by 
densely  packed  zones  of  lymphoid  and  plasma  cells  and 
eosinophiles.  The  epithelial  cells  composing  these  offshoots 
are  irregularly  arranged,  and  show  absence  of  or  atypical 
arrangement  of  prickle  fibrils. 

In  this  lesion  the  picture  indicates  that  differentiation  of 
the  epidermal  cells  into  keratohyaline  and  keratin  has 
ceased  and  that  the  whole  depth  of  cells  is  in  active  growth 
with  beginning  invasion  at  the  base. 

Large  ulcer  from  hand.  The  ulcerated  surface  is  the 
exposed  surface  of  a  vascular  new  growth  of  epidermis, 
atypical  in  arrangement  and  containing  many  mitoses  and 
whorls  of  keratinized  cells.  This  tissue  is  microscopically 
a  typical  epidermoid  carcinoma,  and  there  is  invasion  of  the 
corium  by  slender  processes  of  cells  on  all  sides. 

The  skin  on  each  side  of  the  carcinoma  shows  the  same 
changes  that  have  been  described  in  the  preceding  cases,  i.e., 
rarefication  of  the  corium  beneath  the  epidermis,  atypical 
downgrowths  of  epidermis,  vascular  changes  and  hyaline 
change  of  the  collagenous  fibrils  in  the  deep  layers  of  the 
corium. 

Tissue  from  the  chest.  This  consists  of  a  semi-circular 
piece  of  tissue  the  convex  border  of  which  is  covered  by 
epidermis,  and  measures  fourteen  millimeters  long.  On 
each  side  of  the  center  of  the  epidermis  is  an  area  of  new 
growth  very  similar  to  that  from  the  ulcer  of  the  hand. 
These  areas  are  three  to  four  millimeters  long  and  consist  of 
a  vascular  new  growth  of  epithelium  with  whorls  of  kerati- 
nized cells  and  many  mitoses.  There  is  no  definite  covering 
of  epidermis  and  the  surface  is  covered  with  a  few  small 
patches  of  horny  epithelium  and  fibrin.  The  corium  sur- 
rounding these  two  areas  is  infiltrated  in  every  direction. 
The  whole  picture  is  typical  of  epidermoid  carcinoma.  The 
epidermis  between  these  two  areas  and  outside  of  them  is 
thick  with  large  processes.  The  corium  and  vessels  show 
the    same    changes    that    have    been    described     above.     In 


HISTOLOGY   OF   CHRONIC    X-RAY   DERMATITIS.         433 

addition  to  the  two  areas  of  carcinoma  there  is  one  small 
area  of  marked  downgrowth  of  the  epidermis,  the  processes 
of  which  are  surrounded  by  masses  of  lymphoid  and  plasma 
cells  (Fig.  15).  From  one  of  these  processes  there  is  a 
large  mass  of  cells,  containing  many  mitoses,  extending  into 
the  corium  (Fig.  20).  Smaller  masses  project  from  two 
adjacent  epidermal  processes.  All  are  surrounded  by 
densely  packed  zones  of  lymphoid  and  plasma  cells.  It  is 
evident  that  the  process  here  is  the  beginning  of  a  growth 
similar  to  the  larger  ones  in  the  same  piece  of  tissue.  A 
series  of  twenty-seven  sections  through  this  region  excluded 
the  possibility  of  this  appearance  being  due  to  a  tangential 
section  of  a  larger  growth. 

Case  VI.  (W.  W.  G.,  Case  III.,  Dr.  Porter).  —  Male ;  41 
years.  Began  work  with  the  X-rays  in  1897.  I"  1900  he 
suffered  from  X-ray  dermatitis  on  the  dorsum  of  the  right 
hand,  which  after  healing  left  the  skin  dry  and  reddened. 
In  1901  the  nail  of  the  index  finger  was  removed  because  of 
severe  pain.  In  1903  the  characteristic  telangiectases  and 
keratoses  developed.  Persistent  painful  ulceration  neces- 
sitated the  amputation  of  several  fingers  and  numerous  areas 
of  skin  between  the  years  1903  and  1908.  In  August,  1908, 
the  small  lesion  was  excised  from  which  the  following 
description  is  taken. 

The  material  consisted  of  a  circular  piece  of  skin  eight 
millimeters  in  diameter.  The  center  is  covered  with  a  thick 
layer  of  horny  epidermis,  forming  an  elevated  area  five 
millimeters  in  diameter. 

Microscopic  examination.  The  corium  shows  marked 
hyaline  change  of  the  collagenous  fibrils  and  a  great  increase 
in  elastic  fibers.  There  are  few  connective  tissue  cells  to  be 
found  except  immediately  beneath  the  epidermis  where  the 
corium  is  less  dense  in  structure  and  where  there  are  minute 
foci  of  necrosis  and  infiltration.  Small  arteries  show  thick- 
ening of  the  intima  due  to  a  layer  of  dense  collagenous 
material    between  the    media    and  endothelium.     There   are 


434  WOLBACH. 

a  few  normal  coil  glands  but  many  showing  atrophy.  The 
very  few  hair  bulbs  and  shafts  which  are  in  the  sections  are 
normal. 

The  corium  immediately  beneath  the  epidermis  shows 
traces  only  of  the  papillae  in  the  form  of  very  slight  slender 
elevations  extending  into  the  epidermis.  These  papillae 
contain  each  a  single  large  capillary  with  prominent  endo- 
thelium. The  epidermis  is  thick  and  forms  an  even  layer 
except  where  interrupted  by  the  small  papillae.  In  many 
places,  however,  there  are  large  capillaries  running  high  up 
into  the  epidermis,  surrounded  by  a  thin  zone  of  refractive 
hyaline  collagenous  material.  The  thickness  of  the  epider- 
mis is  chiefly  due  to  increase  in  the  prickle  cell  layer.  The 
stratum  lucidum  is  of  increased  thickness.  The  granular 
layer  is  not  demonstrable.  The  horny  layer  is  very  thick 
and  consists  of  a  fused  mass  of  incompletely  keratinized 
cells  in  which  the  nuclei  are  large  and  easily  visible  (acan- 
thosis). In  places  where  the  corium  contains  areas  of  frag- 
mented collagenous  material  and  masses  of  lymphoid  and 
plasma  cells,  there  are  shallow  downgrowths  of  the  epidermis. 
The  cells  of  these  downgrowths  extend  laterally  between 
bundles  of  hyaline  collagenous  material. 

In  addition  to  the  above  cases,  sections  prepared  at  the 
Massachusetts  General  Hospital  of  a  case  reported  by  Dr. 
C.  A.  Porter  (Annals  of  Surgery,  November,  1907)  have 
been  studied  (Case  XIX.,  Dr.  Porter's  paper,  this  issue). 
The  sections  were  described  for  the  above  report  by  Dr.  C.  J. 
White,  who  paid  particular  attention  to  changes  in  the 
epidermis. 

The  series  of  sections  include  thirty  lesions  removed  in 
eight  or  nine  different  operations. 

All  of  the  changes  described  in  detail  from  the  tissues  of 
the  six  cases  reported  above  have  been  found  in  the  tissues 
from  this  one  individual.  This  man,  according  to  Dr.  Porter 
and  corroborated  by  the  sections,  had  ten  different  epider- 
moid carcinomata  removed  in  five  years. 

This    case,  therefore,   furnishes    strong    evidence   that  the 


HISTOLOGY    OF    CHRONIC    X-RAY    DERMATITIS.  435 

changes    described    in    the    epidermis    are    progressive    and 
develop  into  carcinomata. 

SUMMARY    OF   THE   HISTOLOGICAL   CHANGES. 

The  changes  that  have  been  found  in  the  cases  described 
can  be  summarized  best  under  separate  headings  as  follows  : 
connective  tissue,  smooth  muscle,  blood  vessels,  and  epider- 
mis with  its  appendages 

I.  Changes  in  the  connective  tissue  of  tJie  corium  and  sub- 
cntajieons  tissue.  —  The  most  conspicuous  of  the  constant 
changes  in  the  corium  are  the  rarefication  immediately 
beneath  the  epidermis  and  the  great  density  of  the  connec- 
tive tissue  deeper  down  (Figs,  i  to  6).  The  loose  textured 
connective  tissue  immediately  below  the  epidermis  is  best 
interpreted  as  imperfect  repair  of  degenerated  connective 
tissue  due  at  first  to  the  direct  action  of  the  X-rays.  The 
imperfect  repair  and  subsequent  degenerations  are  due  most 
probably  to  the  vascular  lesions.  The  presence  of  degener- 
ated hyaline  collagenous  material  throughout  the  depth  of 
the  corium  must  be  a  direct  effect  of  the  rays.  That  this 
modified  collagenous  material  represents  inert  or  dead  tissue, 
if  such  a  term  may  be  used  in  speaking  of  intercellular  sub- 
stance, is  proved  not  only  by  the  physical  appearance  and 
staining  reactions,  but  also  by  the  presence  of  young  con- 
nective tissue  cells  surrounded  by  normal  appearing  collage- 
nous fibrils  between  the  masses  of  this  dense  collagenous 
material  (Figs.  10  and  ii).  Further  proof  is  furnished  by 
the  finding  of  isolated  masses  of  similar  material,  identical  in 
appearance  and  staining,  in  the  granulation  tissue  below  the 
ulcerations.  This  diffuse  aseptic  necrosis  of  connective  tissue 
and  resulting  dift'use  proliferation  of  connective  tissue  cells  is 
probably  directly  responsible  for  the  obliteration  of  blood 
and  lymph  vessels.  Repeated  exposures  to  the  X-rays  is  in 
this  way  accountable  for  the  production  of  successive  depos- 
its of  collagenous  material,  and  this  is  the  only  satisfactory 
explanation  of  the  great  density  of  the  deep  corium.  Areas 
of  fibrin  in  tissues  many  months  after  the  last  exposure  to 
the  rays  prove  that  the  lesions  are  slowly  progressive.     The 


436  WOLBACH. 

marked  increase  of  elastic  tissue  almost  constantly  found  is 
difficult  to  account  for.  That  a  new  formation  occurs,  may  be 
proved  by  the  association  of  delicate  elastic  fibers  with  new 
connective  tissue  cells.  Coarse  fibrils  present  may  represent 
remains  from  successive  crops  of  connective  tissue  which 
have  undergone  degeneration.  The  presence  of  many 
degenerated  fibers  suggests  this  explanation.  The  question 
needs  more  elaborate  study  for  its  solution  than  the  scope  of 
this  paper  will  permit. 

Many  of  the  connective  tissue  cells  in  the  rarefied  corium 
are  of  extraordinary  size  with  large  processed  nuclei  (Fig. 
7).  Many  have  numerous  small  nuclei  each  containing  a 
particle  of  chromatin.  These  cells  may  be  distinguished 
from  endothelial  cells  by  the  presence  of  fibroglia  fibrils. 
Apparently  they  do  not  form  collagenous  material.  With 
the  methylene  blue  and  eosin  stain  the  protoplasm  stains  a 
deep  blue.  A  few  are  vacuolated.  Similar  large  cells  are 
found  in  the  fat  lobules  of  the  subcutaneous  tissue,  where 
the  fat  is  undergoing  resorption.  The  interpretation  is  that 
these  cells  are  the  result  of  proliferation  under  conditions  of 
poor  nutrition.  As  they  are  found  only  where  there  is  mul- 
tiplication of  connective  tissue  cells,  they  must  represent 
imperfect  growth  and  differentiation. 

2.  Changes  in  the  smooth  ninscle.  —  The  large  size  of  the 
arrector  pili  muscle  and  the  thickness  of  the  nuclei  of  arteries 
has  led  some  authors  (Unna  and  Wyss)  to  speak  of  the  con- 
dition as  one  of  smooth  muscle  hypertrophy.  In  the  present 
study  degenerative  changes  were  always  present  and  the 
large  size  of  the  smooth  muscle  cells  is  due  to  vacuolization 
(noted  by  numerous  authors)  and  distension  of  the  cell  with 
hyaline  material,  the  latter  easily  demonstrable  by  the  phos- 
photungstic  acid  hematein  stain.  In  cases  of  long  duration 
only  atrophic  remains  of  the  arrector  pili  muscles  were  found, 
showing  that  the  changes  noted  are  unquestionably  degenera- 
tive. This  degeneration  of  smooth  muscle  will  be  considered 
again  in  connection  with  vessel  changes. 

3.  Changes  in  the  vessels.  —  The  study  of  lymphatics 
in    skin,    which    is    the    seat    of    chronic    changes,    presents 


HISTOLOGY   OF   CHRONIC   X-RAY   DERMATITIS.         437 

extraordinary  difficulties  when  attempted  by  the  methods  em- 
ployed in  this  study.  The  unquestionable  obliteration  of 
blood  capillaries  and  the  extreme  difficulty  of  demonstrating 
lymphatics  in  the  tissues  studied  makes  the  assumption  war- 
rantable that  there  also  has  been  obliteration  of  lymphatics. 

The  changes  in  blood  vessels  on  the  other  hand  are  easily 
demonstrable.  The  telangiectases  apparently  develop  from 
preexisting  capillaries,  those  of  the  papillae  of  the  corium 
(Figs.  2,  3,  4,  and  5).  Various  stages  of  dilatation  of  these 
capillaries  can  be  seen  in  connection  with  other  changes,  in 
lesions  of  varying  intensities  from  different  cases.  The 
mechanism  of  their  formation  cannot  be  discovered  through 
histological  examination,  though  obliterative  changes  in  the 
larger  vessels  and  in  the  deeper  anastomosing  capillaries 
must  play  a  part.  Another  factor  to  be  taken  into  considera- 
tion is  possible  traction  upon  the  capillary  walls  exerted  by 
contracting  connective  tissue.  New  collagenous  material  is 
frequently  laid  down  between  the  meshes  of  older  degenerated 
fibrous  tissue  and  undoubtedly  must  undergo  some  contrac- 
tion before  the  dense  stage  is  reached.  Thrombosis  of  these 
telangiectases  is  common  and  is  usually  associated  with 
necrosis  of  the  tissue  immediately  surrounding  as  well  as  of 
the  lining  endothelium.  Obliteration  of  capillaries  by  prolif- 
eration of  endothelium  is  a  fairly  constant  finding  in  most  of 
the  cases  studied. 

The  obliterative  changes  in  the  veins  and  arteries  are 
manifested  chiefly  in  a  great  increase  of  connective  tissue 
beneath  the  endothelium  and  in  marked  thickening  of  the 
media.  In  the  arteries  there  is  disappearance  of  the  elastic 
lamina  and  a  substitution  of  a  thick,  irregular  band  of  hyaline 
collagenous  material.  The  thickened  intima  is  composed  of 
connective  tissue  with  much  collagenous  intercellular  sub- 
stance. The  endothelium  is  often  composed  of  swollen  and 
vacuolated  cells  which  occasionally  form  tufts  of  ceils  project- 
ing into  the  lumen. 

The  thickening  of  the  media  is  due  to  an  increase  of  con- 
nective tissue.  By  means  of  the  stains  employed  it  is  possi- 
ble to  demonstrate  large  fibroblasts  and  abundant  collagenous 


438  WOLBACH. 

material  between  the  smooth  muscle  cells.  The  latter  show 
varying  degrees  of  atrophy  and  degeneration — hyaline 
change  and  vacuolization  (Figs.  17,  21,  and  22). 

The  finding  of  mitotic  connective  tissue  cells  in  one  case 
(No.  III.)  four  years  after  the  last  exposure  illustrates  the 
extreme  slowness  of  this  process,  as  well  as  its  progressive 
character.  In  advanced  cases  of  obliterative  endarteritis  the 
media  is  wholly  replaced  by  connective  tissue  with  many 
large  branching  fibroblasts.  In  all  of  the  cases  studied  oblit- 
erative changes  have  been  found  in  some  of  the  vessels,  though 
normal  vessels  are  usually  also  present. 

4.  Changes  in  the  epidermis.  —  Except  over  foci  of  acute 
degeneration  of  the  corium,  hypertrophy  of  the  epidermis  is 
a  constant  finding.  The  hypertrophy  in  most  cases  is  in  the 
form  of  a  fairly  uniform  thickening  of  the  epidermis.  In 
other  cases  there  are  local  more  marked  hypertrophies  taking 
the  form  of  keratoses  and  downgrowths  (Figs,  13,  14,  15,  16, 
and  17).  In  nearly  every  case  there  are  numerous  areas 
where  the  proliferation  of  epidermis  seems  unquestionably  to 
be  due  to  disappearance  of  connective  tissue  in  the  corium 
which  has  not  the  power  to  repair  itself  (Figs.  12,  4,  and  5). 
The  downgrowth  of  epidermis  is  analogous  to  the  growth  of 
the  corneal  epithelium  following  an  incised  wound  of  the 
cornea,  or  even  gaping  wounds  of  the  cornea  such  as  may  be 
made  by  plowing  beneath  the  corneal  epithelium  with  a 
sharp  triangular-shaped  needle  (Glover's  needle). 

Extensive  downgrowths  of  epidermis  are  found,  in  several 
cases,  having  all  of  the  characteristics  of  carcinoma  with  and 
without  evidence  of  invasion.  The  cases  showing  metastatic 
growths  have,  not  been  included  in  this  report.  Growth  of 
epidermis  into  thrombosed  telangiectases  is  unusual  and  must 
be  interpreted  as  indicative  of  increased  powers  of  growth 
(Figs.  8  and  9).  Generally  the  epithelial  downgrowths  are 
surrounded  by  zones  of  dense  infiltration  with  lymphoid  and 
plasma  cells,  cosinophiles  and  polymorphonuclear  leucocytes. 
The  epidermis  where  there  is  evidence  of  greatest  prolifera- 
tion of  the  basal    layers   has    a   thin  horny  layer,  as  if  the 


HISTOLOGY   OF   CHRONIC    X-RAY   DERMATITIS.         439 

whole  capacity  of  the  epitheHum  was  taxed  to  preserve  its 
continuity  (Fig,  2). 

In  general  the  increased  thickness  of  the  epidermis  and  the 
production  of  wart-like  growths  or  keratoses  and  down- 
growths  is  best  explained  as  the  result  of  constant  active 
proliferation  called  for  by  the  constant  production  of  small 
defects  in  the  underlying  corium.  In  Case  V.  the  ulcer  from 
the  hand  shows  undoubted  signs  of  malignancy. 

Complete  absence  of  hair  follicles,  sebaceous  and  coil 
glands  is  the  rule  in  cases  of  long  duration.  In  less  marked 
cases  atrophic  glandular  structures  were  found.  In  no  case 
was  there  evidence  of  proliferation  of  any  of  the  skin  append- 
ages. Coil  glands  were  often  found  in  regions  where  there 
was  total  absence  of  hair  follicles  and  sebaceous  glands. 

In  the  description  of  cases  minute  cell  changes  have  been 
omitted.  The  finding  in  the  epidermis  of  cells  with  extraor- 
dinarily large  nuclei  with  evidences  of  direct  division  into 
several  smaller  nuclei  was  of  frequent  occurrence.  Such 
cells  are  most  often  in  small  downgrovvths  or  in  compact 
masses  of  cells  inserted  in  the  basal  layers.  This  change  and 
others  such  as  irregularity  in  size,  greater  affinity  for  basic 
stains  and  confused  arrangement  of  prickle  fibrils  have  been 
regarded  as  concomitant  with  proliferative  and  degenerative 
changes.  Possibly  the  finding  of  such  changes  in  down- 
growths  and  isolated  masses  of  cells  has  a  slight  value  as 
evidence  of  altered  function  and  increased  proliferative 
power. 

Discussion.  —  All  of  the  cases  of  this  series  present  only 
late  effects  of  single  or  repeated  X-ray  exposures ;  and  it  is 
therefore  beyond  the  scope  of  this  paper  to  give  a  complete 
account  of  the  effects  of  X-rays  upon  human  skin.  The 
chronic  changes  described  were  necessarily  preceded  by 
acute  changes,  which  were  the  immediate  result  of  the 
X-ray  exposures.  No  complete  investigation  of  the  acute 
changes  has  as  yet  been  made.  As  many  of  the  changes 
described  in  this  paper  have  been  previously  described, 
a  short  review  of  the  most  important  papers  is  included. 


440  WOLBACH. 

Gassmann  (Archiv.  f.  Dermat.  u.  Syphilis,  1904,  Heft  I.) 
described  the  vessel  changes  produced  in  rabbits.  He 
exposed  rabbits  until  ulcers  of  one  month's  duration  had 
been  produced  and  found  the  following  changes  in  the 
arteries :  The  muscularis  showed  a  sieve-like  meshwork  due 
to  vacuolization.  The  intima  was  thickened  and  broken  up, 
the  elastica  was  fragmented  and  the  endothelium  was 
thickened  and  in  places  heaped  up  two  or  three  cells  deep. 
He  claims  to  have  demonstrated  obliteration  of  lymphatics 
through  excessive  proliferation  of  endothelium. 

Linser  (Fortschritte  auf  dem  Gebiete  der  Rontgenstrahlen 
No.  8,  1904—5)  excised  human  skin  at  varying  intervals 
while  the  patient  was  receiving  treatment  for  lupus.  At  the 
end  of  four  days  there  were  vessels  occluded  by  thrombi. 
The  endothelium  was  absent  in  places  and  in  other  places 
swollen  and  projecting  into  the  lumen.  The  media  was 
"  broken  up  "  and  "  fissured."  There  was  slight  perivascular 
infiltration  Avith  "  round  cells."  At  eight  days  thrombosed 
vessels  were  most  numerous  and  the  perivascular  infiltration 
was  most  marked.  At  sixteen  days  there  was  beginning 
thickening  of  the  intima.  The  breaking  up  of  the  media  and 
invasion  by  leucocytes  was  at  its  maximum.  At  twenty  days 
there  was  marked  thickening  of  the  intima  due  to  pure  con- 
nective tissue  without  elastic  fibers.  Many  vessels  were 
completely  obliterated.  At  the  end  of  thirty  days  the 
"  inflammatory  changes  "  were  absent.  The  arteries  showed 
typical  thickening  of  the  intima  with  newl}'  formed  elastic 
fibers,  giving  to  the  vessels  a  shrunken,  irregular  form  with 
polyp-like  projections  into  the  lumen.  Linser  concludes 
that  the  epithelium  is  not  primarily  affected  even  after  severe 
exposure.  The  only  changes  that  he  found  was  an  increase 
of  pigment  in  the  Malpighian  layer.  The  hairs  and  glands 
remained  normal. 

Unna  (Fortschritte  auf  dem  Gebiete  der  Rontgenstrahlen 
No.  8,  1904—5)  reported  a  study  of  four  cases  of  chronic 
X-ray  dermatitis.  He  emphasized  the  latent  period,  which 
varied  from  a  few  months  to  two  or  three  years,  and  in  view 
of  the  experimental  work  already  done  upon  animals  stated 


HISTOLOGY    OF    CHRONIC    X-RAY    DERMATITIS.  44 1 

that  the  etiology  of  the  lesions  was  unquestionable.  The 
origin  of  the  telangiectasis  is  discussed  at  length.  Unna 
says  that  a  deep  obliterating  endophlebitis  would  explain  the 
production  of  the  telangiectasis,  but  that  this  has  not  been 
proved.  The  arterial  obliteration  does  not  explain  it.  Unna 
agrees  with  Baer  and  Linser  (Miinch.  Med.  Wochenschr. 
No.  23,  1904)  in  believing  that  the  blood  transforms  the 
X-rays  into  a  form  of  energy  that  is  injurious  to  the  vessel 
walls.  This  he  says  is  supported  by  the  fact  that  tissues 
rich  in  blood  as  granulation  tissue,  either  exposed  or  covered 
by  epithelium,  is  more  affected  by  the  X-rays  than  is  normal 
tissue. 

The  microscopic  appearance  of  the  tissues  is  given  in  great 
detail.  Great  stress  is  laid  upon  the  density  of  the  connective 
tissue  of  the  cutis,  which  is  attributed  to  degenerative  changes 
following  edema.  In  one  case  he  describes  atypical  growth 
of  epithelium  at  the  edge  of  an  ulcer,  which  he  believed  to  be 
a  beginning  carcinoma.  He  did  not  find  changes  in  the 
larger  vessels  of  the  deep  cutis  and  hypoderm.  As  a  possi- 
ble cause  of  the  telangiectasis  he  suggests  tension  of  the 
smooth  muscle  bundles  called  into  play  by  the  general 
atrophy  of  connective  tissue  and  by  the  disappearance  of 
intercellular  substance  between  the  muscle  cells.  The  kera- 
toses are  manifestations  of  the  atrophy  of  the  epidermis, 
analogous  to  those  occurring  in  senile  changes,  sailor's  car- 
cinoma, and  xeroderma  pigmentosum.  In  retrospectfon  he 
says  that  the  effects  of  the  X-rays  are  not  limited  to  the 
vessels,  but  affect  all  parts  of  the  skin,  and  that  there  is  no 
indication  of  an  especial  susceptibility  of  the  epidermis.  The 
epidermis  becomes  markedly  cornified,  in  part  hypertrophic 
and  predisposed  to  cancer,  in  part  atrophic.  The  appendages 
atrophy,  first  of  all  the  hair  follicles  and  sebaceous  glands. 
In  the  cutis  there  is  a  marked  chronic  interstitial  edema 
which  loosens  and  rarefies  the  collagen  and  leads  to  atrophy 
of  the  elastic  fibers.  The  smooth  muscle  alone  becomes 
thickened.  Unna  emphasizes  the  difificulty  of  obtaining  good 
sections  because  of  the  great  density  of  the  cutis. 

Schumann's     (Archiv.     f.     Klin.    Chirurg.     Berlin,     1907, 


442  WOLBACH. 

LXXXIV.,  Heft  3)  description  of  cases  differs  from  that  of 
Unna's  only  in  the  statement  that  there  was  proliferation  of 
the  sweat  glands  producing  tortuous  solid  chains  of  cells. 
He  states  that  the  chronic  X-ray  dermatitis  predisposes  to 
carcinoma  and  points  out  similarities  between  it  and  other 
conditions  followed  by  carcinoma  such  as  xeroderma  pig- 
mentosum, senile  changes,  and  Unna's  carcinoma  of  sailors. 

VVyss  (Beitrage  z.  klin.  Chir.  Tiibingen,  1906,  XLIV. ) 
argues  for  the  connection  between  vessel  changes  and  the 
origin  of  carcinoma  and  says  that  he  is  the  first  to  insist 
upon  this  point.  Following  Ribbert's  ideas  that  connective 
tissue  changes  precede  carcinoma  of  the  skin,  and  bring 
about  isolation  of  epithelial  cells,  he  comes  to  the  following 
conclusions  :  That  the  carcinoma  cell  is  one  isolated  from 
the  rest  of  the  body  through  the  gradual  withdrawal  of  nutri- 
tion owing  to  successive  obliteration  of  vessels  ;  that  the 
cells  thus  gradually  acquire  greater  capacity  for  securing 
nutrition  and  finally  become  capable  of  living  at  the  expense 
of  other  cells.  He  claims  that  similar  vascular  changes  pre- 
cede many  kinds  of  carcinomata  associated  with  peculiar 
practises  or  occupations. 

In  a  subsequent  paper  upon  the  origin  of  carcinoma 
(Deutsch,  Archiv.  f.  Chirurgie,  Leipzig,  XCIH.,  Heft  6), 
Wyss  offers  the  evidence  furnished  by  the  X-ray  carcinomata 
and  the  results  of  a  study  of  fifty  early  carcinomata  in 
support  of  Ribbert's  theories.  In  all  cases  he  insists  that 
vascular  changes  are  primary. 

Lindenhorn  (Beitrage  zur  klin.  Chir.  Tiibingen,  LIX., 
Heft  2)  has  collected  twenty-nine  cases  of  X-ray  tumors, 
most  of  them  carcinoma  and  very  malignant.  The  two 
cases  which  he  adds  were  in  lupus  patients  treated  with  the 
X-rays.  The  vessel  changes  described  by  him  were  limited 
to  the  media.  In  general  he  corroborates  the  work  of  VVyss 
and  others,  but  states  that  the  condition  is  essentially  that 
of  premature  senescence. 

Porter  and  White  (Annals  of  Surgery,  November,  1907) 
contribute  the  only  important  paper  on  the  subject  from  this 
country.     The    histological    changes    are    described   without 


HISTOLOGY    OF   CHRONIC   X-RAY   DERMATITIS.         443 

attempt  at  a  summary.  Particular  attention  is  paid  to  the 
fine  changes  in  the  epidermis.  Obliterative  changes  of  large 
veins  and  arteries  are  noted  as  well  as  obliteration  of  capil- 
laries by  proliferation  of  the  endothelium.  Very  excellent 
objective  descriptions  are  given  of  the  keratoses  and  epithe- 
lial hypertrophies  and  of  the  telangiectases.  Several  typical 
epidermoid  carcinomata  are  described  as  such,  in  the  case 
presented  by  Porter. 

GENERAL   SUMMARY. 

The  value  of  this  study  of  cases  here  reported  is  largely 
dependent  upon  the  wide  range  of  time  represented  after 
receipt  of  the  injuries  and  in  the  varying  amounts  of  expos- 
ure to  the  X-rays  received  in  the  different  cases.  A  sequence 
of  changes  can  be  seen  which  previous  studies  have  not 
brought  out.  The  immediate  effects  of  the  X-rays,  of  course, 
are  not  included,  but  the  early  changes  can  be  inferred  from 
the  nature  of  the  chronic  changes  and  the  possibilities  agree 
with  the  results  obtained  by  Linser  upon  human  skin  and 
by  others  upon  animals. 

The  most  important  fact  brought  out  in  the  present  study 
is  that  after  sufficient  injury  has  been  done  complete  repair 
does  not  take  place.  There  are  in  every  case  active  pro- 
cesses going  on,  and  when  we  consider  that  some  of  the 
cases  had  received  the  last  exposure  two  to  four  years  before 
excision,  this  fact  becomes  of  great  importance.  Not  only 
are  degenerative  and  r-eparative  changes  constantly  taking 
place  in  the  corium,  but  the  occurrence  of  progressive  vascu- 
lar lesions  is  proved  by  the  findings  in  the  media  of  arte- 
ries of  young  fibroblasts  and,  in  one  instance,  mitosis  of 
connective  tissue  cells. 

All  the  changes  primarily  produced  by  the  X-rays  are 
probably  degenerative  in  character.  Normal  repair  is  im- 
possible after  a  certain  amount  of  injury  has  been  done 
because  of  the  vascular  changes.  Thus  there  is  constant 
degeneration  of  the  tissue  in  foci  and  constant  efforts  at 
repair.       The     non-vascular    rarefied     corium     beneath    the 


444  WOLBACH. 

epidermis  is  an  example  of  imperfect  repair.  The  finding  of 
necrotic  foci  here  and  deeper  in  the  corium,  many  months 
and  even  years  after  the  last  X-ray  exposure,  is  conclusive 
proof  of  the  vascular  origin  of  the  degenerations.  If  the 
focus  of  degeneration  is  small,  ulceration  does  not  occur. 
The  continuity  of  the  epidermis  is  preserved  through  down- 
ward proliferation,  and  thus  a  deeper  stratum  of  connective 
tissue  is  reached  better  able  to  maintain  nutrition.  That 
proliferative  changes  in  the  epidermis  are  constantly  going 
on  in  these  cases  is  proved  by  the  character  of  the  cells  of 
the  basal  layers  and  the  presence  of  many  mitoses.  In 
many  instances  the  growth  into  such  foci  of  degeneration 
has  been  observed,  and  even  into  thrombosed  telangiectases. 
Other  evidences  of  impaired  nutrition  of  the  skin  are  the 
atrophy  of  the  glands  and  the  absorption  of  fat  tissue  and 
replacement  by  connective  tissue. 

The  large  size  of  the  arrector  pili  muscles  is  not  due  to 
hypertrophy,  but  to  swelling  of  the  cell  and  fusion  of  the 
myoglia  fibrils.  In  cases  of  greatest  duration  these  muscles 
are  entirely  replaced  by  connective  tissue.  The  same  degen- 
erative changes  in  the  smooth  muscle  of  the  media  of  vessels 
account  for  the  vacuolization  and  later  the  replacement  of 
muscle  tissue  by  connective  tissue. 

The  obliteration  of  small  vessels  and  capillaries  probably 
taT<es  place  slowly  and  continuously  owing  to  the  swelling 
of  collagenous  material  and  proliferation  of  connective  tissue. 
Endothelial  proliferation  is  possibly  a  primary  cause  of 
capillary  obliteration.  It  would  also  occur  in  capillaries 
occluded  from  other  causes.  Excessive  infiltration  of  the 
corium  by  lymphoid  and  plasma  cells  undoubtedly,  as  Wyss 
suggests,  helps  to  interfere  with  nutrition  of  epithelium  by 
pressure  upon  capillaries. 

Epithelial  proliferation  is  a  constant  finding  over  foci  of 
degeneration  in  the  corium.  Ulceration  occurs  only  if  the 
degenerated  area  is  too  large  to  be  bridged  over  by  the  epi- 
dermis. It  is  probable  that  long  continued  proliferative 
processes  are  responsible  for  the  hypertrophy  of  the  epi- 
dermis.    Downgrowth  of  epidermis  takes  place  to  fill  small 


HISTOLOGY    OF   CHRONIC    X-RAY   DERMATITIS.  445 

gaps  in  the  corium.  This  property  of  downgrowth  to  fill 
gaps  in  the  epidermis  as  well  as  the  growth  of  epidermis 
into  thrombosed  telangiectases  must  be  taken  as  evidence  of 
increased  vitality  of  the  epidermis.  Some  downgrowths,  of 
a  size  discoverable  only  with  the  microscope,  show  all  of  the 
characteristics  of  epidermoid  carcinoma  including  the  pres- 
ence of  whorls  of  cornified  cells  and  evidence  of  invasion 
between  bundles  of  connective  tissue.  There  are  larger  epi- 
thelial downgrowths  which  are  apparently  limited  in  their 
growth.  The  depth  seems  to  be  determined  by  the  reach- 
ing of  viable  connective  tissue.  In  the  same  case  all  degrees 
of  epithelial  hypertrophies,  downgrowths,  and  keratoses  may 
occur,  and  also  growths  which  are  histologically  carcinoma 
and  which  grow  slowly  and  invade  normal  tissues.  Although 
this  series  does  not  include  cases  in  which  metastases  have 
occurred,  such  cases  are  too  well  known  to  admit  of  any 
doubt  as  to  the  malignancy  of  the  slowly  growing  invasive 
tumors  such  as  are  described  in  Case  V. 

The  evolution  of  X-ray  carcinoma  from  the  smaller  lesions, 
scaly  patches,  and  keratoses  has  been  constantly  observed  in 
the  clinical  study  of  reported  cases  so  that  there  can  be  no  doubt 
that  the  smaller  epithelial  growths  described  in  this  paper  are 
the  starting  points  of  the  malignant  growths  and  especially 
is  this  true  in  those  cases  where  similar  lesions  had  already 
developed  into  ulcerations  which  microscopically  were  unques- 
tionable carcinomata.  This  evidence  is  of  course  wholly 
clinical,  but  the  observers  of  these  cases  have  been  for  the 
greater  part  prominent  physicians  who  often  were  caring  for 
their  colleagues.  Because  the  subjects  of  these  experi- 
mental carcinomata  have  been  men  instead  of  animals  and 
the  observers  not  laboratory  workers  does  not  invalidate  the 
evidence.  And  this  evidence  is  overwhelming  that  the  car- 
cinomata are  produced  by  changes  following  severe  X-ray 
exposures.  As  Wyss  has  already  insisted,  the  X-ray  carci- 
noma is  the  first  experimental  carcinoma. 

What  then  gives  rise  to  the  carcinoma?  Is  it  the  direct 
action   of  the  X-rays  upon  the  epithelium   or  is  it  the  result 


446  WOLBACH. 

of  changes  produced  in  the  deeper  tissues?  All  the  evidence 
advanced  by  Unna  and  by  Wyss  and  that  found  in  the  pres- 
ent study  of  cases  proves  that  the  epidermis  is  the  least 
susceptible  of  the  tissues  of  the  skin  to  direct  injury  by  the 
X-rays.  Even  if  this  were  not  the  case  the  long  "  latent" 
period  elapsing  between  the  last  exposure  to  the  rays  and 
the  appearance  of  proliferative  changes  in  the  skin  could  not 
be  accounted  for  except  by  assuming  that  the  repeated 
action  of  the  rays  excites  proliferative  powers  which  remain 
dormant  for  months  to  years.  But  we  do  know  that  during 
this  "  latent "  period  the  epidermis  is  subject  to  changed 
conditions  involving  marked  alterations  in  the  character  of 
the  connective  tissue  supporting  it  and  presumable  marked 
changes  in  the  nutrition  of  the  cells.  And  also  that  constant 
proliferative  changes  are  necessitated  on  the  part  of  the  epi- 
dermis in  order  to  preserve  its  integrity.  We  must  then 
conclude  that  the  factors  responsible  for  the  acquisition  of 
great  powers  to  proliferate  and  eventually  the  properties  of 
malignancy,  are  those  furnished  by  the  changes  in  blood 
supply  and  in  the  connective  tissue.  This  theory  is  sup- 
ported very  completely  by  the  microscopic  appearances, 
especially  in  those  instances  where  we  find  evidence  of  active 
proliferation  of  epidermis  but  incomplete  or  no  differentia- 
tion into  horny  epithelium.  The  finding  of  growth  of  epi- 
dermis into  fibrin  thrombi  and  into  areas  of  dense  bloodless 
collagenous  material  seems  to  be  evidence  of  increased  pow- 
ers of  proliferation.  Such  reasoning  as  the  above,  based  as 
it  is  upon  microscopical  findings  and  upon  observed  gross 
changes  in  the  living,  leads  to  the  conclusion  that  a  slow 
augmentation  of  the  growth  power  is  achieved  (attended  with 
a  loss  of  differentiation)  that  finally  results  in  the  ability  of 
the  epithelial  cells  to  derive  their  sustenance  at  the  expense 
of  other  living  tissues.  The  fact  that  the  "  virulence  "  or 
growth  power  of  mouse  tumors  may  be  increased  by  suc- 
cessive transplantations  helps  to  make  the  idea  acceptable 
that  a  similar  change  may  occur  in  normal  human  epithe- 
lium. There  must  be  conditions  however  which  call  for,  as 
does    the    chronic   X-ray  dermatitis,   a  continuous  series   of 


HISTOLOGY    OF    CHRONIC    X-RAY    DERMATITIS,  447 

proliferative    processes,  which   in   a   sense   are  auto-inocula- 
tions extending  over  years. 

That  connective  tissue  changes  precede  and  lead  to  the 
development  of  malignant  epithelial  growths  is  essentially  the 
theory  of  Ribbert  as  propounded  in  his  second  Beitrage  zur 
Enstehung  der  Geschwultse.  It  is  essentially  the  conclusion 
reached  by  Goebel  (Zeitschr.  f.  Krebsforschung,  Bd.  Ill,, 
Heft  3)  in  his  study  of  bladder  tumors  associated  with 
Bitharzia  disease.  It  is  the  conclusion  reached  by  Wyss  in 
his  study  of  X-ray  carcinoma  and  of  early  carcinoma  in  gen- 
eral. But  none  of  these  observers  has  described  the  mechan- 
ism leading  to  the  repeated  proliferation  of  the  epidermis. 
Neither  have  they  furnished  microscopic  evidence  of  the  vari- 
ous histological  changes  assumed  to  take  place,  and  the  idea 
conveyed  is  that  the  acquisition  of  malignant  power  takes 
place  suddenly. 

The  acquisition  of  malignant  powers  is  completed  during 
years  of  active  proliferation  accompanied  by  progressive 
impairment  of  nutrition.  This  much  we  have  microscopic 
evidence  for,  and  the  hypothesis  that  the  former  is  a  direct 
sequence  of  the  latter  seems  justifiable. 

Finally  it  is  not  far  removed  from  von  Hansenmann's 
hypothesis  of  tumor  origin, -that  of  anaplasia  wherein  the 
power  of  growth  is  attributed  to  reversion  to  the  stage  of 
proliferative  function  at  the  expense  of  that  of  differentiation. 
The  only  difi^erence  between  this  and  the  theory  suggested 
above  is,  that  in  the  latter  this  power  is  assumed  to  be 
acquired  through  changed  environment. 

The  apparent  demonstration  of  the  origin  of  the  multiple 
carcinomata  of  chronic  X-ray  dermatitis  in  primary  connec- 
tive tissue  changes  and  the  attending  disturbances  of  physi- 
cal and  nutritive  conditions  does  not  speak  for  the  acceptance 
of  the  old  ideas  of  trauma  and  irritation  as  causes  for  the 
origin  of  carcinoma.  In  the  case  of  X-ray  carcinoma  we  are 
dealing  with  injuries  incapable  of  complete  repair  and  there- 
fore progressive  in  character. 

Other  peculiar  forms  of  injury  associated  with  carcinoma, 
such  as  those  occurring-  in  aniline  workers  and  workers  in  the 


448  wo  LB  AC  H. 

various  products  of  combustion  and  distillation  of  coal,  those 
associated  with  certain  diseases,  as  syphilis  (leukoplakia)  and 
lupus,  the  Kangri  carcinoma  of  the  natives  of  Kashimir  and 
"  horn  core"  cancer  of  cattle  in  India,  deserve  the  most  care- 
ful study  to  see  if  the  antecedent  processes  are  similar  to 
those  in  X-ray  cases.  There  is  an  apparent  analogy  in  the 
instances  of  cancer  associated  with  lupus  and  syphilis  in 
that  in  these  diseases  there  are  continuous  connective  tissue 
changes  taking  place  for  years. 

Considering  the  present  great  activity  in  cancer  research  it 
seems  strange  that  more  attention  has  not  been  given  to  this 
field  of  work  and  it  is  the  earnest  hope  of  the  writer  that  this 
paper  may  stimulate  investigation  and  experimental  work 
along  these  lines. 

FThe  writer  is  greatly  indebted  to  Professor  Councilman  for  the  privilege 
of  using  the  photomicrographic  apparatus  of  the  Pathological  Department 
of  the  Harvard  Medical  School,  where  these  photographs  were  made.] 


DESCRIPTION    OF   PLATES. 
Plate  XXXIX. 

Fig.  I.  —  Case  V.  Second  operation.  Skin  from  chest  showing  a 
recent  focus  of  degeneration  in  the  cqrium  beneath  the  epidermis.  Epider- 
mis remains  intact. 

Fig.  2.  —  From  Case  IV.  shows  rarefication  of  the  corium  immediately 
beneath  the  epidermis.  The  lower  strata  of  cells  in  the  epidermis  are 
large  and  are  stained  deeply  with  the  basic  stain.  The  horny  layer  is 
imperfect.  Rapid  multiplication  of  the  epidermis  is  evidenced  by  the  find- 
ing of  many  mitoses.  The  large  capillaries  are  probably  the  precursors 
of  telangiectases. 

Fig.  3.  —  Higher  power  of  Fig.  2  showing  the  character  of  the  basal 
lavers  of  epidermal  cells  and  the  structure  of  the  corium. 

Figs  4  and  5.  —  From  Case  IV.  These  photographs  show  many  large 
telangiectases  and  extreme  rarefication  of  the  corium  beneath  the  epider- 
mis. Fibrinous  thrombi  are  forming  in  several  of  the  telangiectasis. 
The  downgrowth  of  epidermis  in  the  rarefied  corium  is  well  shown. 
This  condition  is  always  accompanied  by  endarteritis  and  endophlebitis. 

Plate  XL. 

Fig.  6.  —  From  Case  IV.  High  power  showing  structure  of  rarefied 
corium  and  a  connective  tissue  cell  in  mitosis. 

Fig.  7.  —  From  Case  IV.  Connective  tissue  cell  from,  rarefied  corium. 
Atypical  cells  of  this  type  and  cells  in  mitoses  are  abundant  in  the  corium 


HISTOLOGY    OF   CHRONIC    X-RAY   DERMATITIS.         449 

beneath  the  epidermis  and  furnish  evidence  of  the  continuous  change 
which  is  reparative  in  nature  and  secondary  to  obliteration  of  vessels. 

Fig.  S.  —  Case  IV.  Low  power  photograph  of  epidermis  growing  into 
thrombosed  telangiectases. 

Fig.  9.  —  High  power  detail  of  Fig.  8. 

Fig.  id. —  Case  I.  shows  hyaline  change  of  collagenous  material  with 
absence  of  connective  tissue  cells. 

Fig.  II. — Case  I.  Hyaline  degenerated  collagenous  material  in  the 
neighborhood  of  vessels  showing  invasion  by  connective  tissue  cells  and 
deposit  of  new  collagenous  material  between  the  masses  of  the  old. 

Plate  XLI. 

Fig.  12.  —  From  Case  IV.  High  power  photograph  of  epidermis  grow- 
ing into  rarefied  corium.  At  this  point  the  corium  is  represented  by  a 
delicate  homogeneous  material  without  cells.  The  epidermis  dips  down  at 
this  point.  The  large  size  and  deep  staining  of  the  cells  is  shown. 
There  is  a  single  mitosis. 

Fig.  13.  —  Case  IV.  High  power  view  of  epidermal  processes  extend- 
ing into  rarefied  corium.  The  process  on  the  left  shows  a  whorl  of  kera- 
tinized cells.  At  the  tip  of  the  process  there  is  marked  lymphoid  and 
plasma  cell  infiltration  and  the  epithelial  cells  are  large  and  irregular  with 
many  mitoses. 

Fig.  14.  —  Case  IV.  Epidermal  process  extending  into  rarefied  corium. 
Evidence  of  independent  growth  shown  by  the  arrangement  of  cells  and 
production  of  epithelial  whorls.  In  the  bar  connecting  the  two  larger 
masses  is  a  nest  Of  cells  with  atypical  arrangement  suggesting  indepen- 
dent growth. 

Fig.  15.  —  Case  V.  From  chest.  Epidermal  process  extending  into 
corium  and  having  the  characteristics  of  the  larger  growths  which  were 
frankly  malignant  in  character. 

Fig.  16.  —  Case  V.  Keratosis  from  back  of  hand  showing  activity  of 
cells  at  the  base,  but  also  the  presence  of  the  different  layers  of  the  epider- 
mis with  dense  horny  layer. 

Fig.  17. —  Case  V.  Keratosis  from  tip  of  nose  showing  absence  of 
differentiation.  The  whole  thickness  of  the  epidermal  process  is  composed 
of  large  cells  of  a  uniform  type.     There  are  many  mitoses. 

Plate  XLII. 

Fig.  18.  —  Case  III.  Obliterated  artery  from  the  deep  corium  showing 
separation  of  muscle  cells  by  connective  tissue.  The  lumen  is  filled  by 
connective  tissue. 

Fig.  19.  —  High  power  view  of  Fig.  16. 

Fig.  20. —  High  power  detail  from  Fig.  15  showing  invasion  of  epider- 
mis into  the  corium. 

Fig.  21. — Low  power  photograph  of  an  obliterated  artery  from  Case 
III. 

Fig.  22.  —  Obliterated  artery  from  Case  V.  At  this  stage  the  muscle 
fibers  have  disappeared  and  there  is  marked  infiltration. 

Fig.  23. —  High  power  detail  of  Fig.  17  showing  large  number  of  mitoses. 

The  Journal  of  Medical  Research,  Vol.  XXI.,  No.  3,  October,  1909. 


JOURNAL  OF  Medical  Research. 


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